中国东北地区精液异常男性不育患者的遗传学因素分析
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摘要
不孕不育是指适龄夫妇婚后1年以上未采取任何避孕措施有规律性生活而仍未受孕。20世纪初期,大多数人认为不孕不育由女性因素所致。而今,事实证明,在不孕不育病例中约一半与男性有关。导致不孕不育因素较为复杂,从遗传性因素到性交障碍均可以影响男性的生育能力。其中,遗传因素约占不育的15-30%。
遗传因素影响男性的生育能力,包括染色体核型异常和Y染色体微缺失。遗传所致不育男性临床表型多样,有些男性射出精液中完全没有精子(无精子症),还有一些男性射出精液中仅有少量精子。为什么遗传所致的不育男性会有不同的临床表型?精液质量异常和遗传因素之间存在什么样的关系?为了回答这些问题,我们对中国东北的1384例不育男性进行了遗传因素分析。这些患者按精液常规结果分为693例无精子症患者和691例精液质量差的患者。此外,50例年龄在24-37岁之间的正常生育男性作为对照。我们通过G显带技术进行染色体核型分析,通过多重PCR技术进行Y染色体微缺失检测,通过电化学免疫荧光方法检测激素水平。最终,我们对临床和实验室结果进行分析来研究精液质量异常和遗传因素之间的关系。本研究经吉林大学白求恩第一医院伦理委员会同意。
结果：
1.无精子症患者相关结果
1.1中国东北无精子症患者中,核型异常比例为23.52%(163/693)。其中,Klinefelter综合征(KS)最为常见(17.75%),其次为染色体多态性(3.32%)和易位(0.72%)
1.2在无精子症患者中,KS和易位携带者的睾丸体积明显小于对照组,而多态和倒位患者睾丸体积和对照组相比没有明显差异。
1.3在无精子症患者中,多态和KS组精浆抑制素B水平明显低于对照组,易位组果糖水平明显高于对照组。KS患者和其他异常核型患者相比精浆生化水平无明显差异。
1.4相比于对照组,多态和KS患者FSH、LH和E2水平升高,而易位和倒位患者其PRL、FSH、LH和E2水平变化不大。值得注意的是,所有染色体异常患者其T和T/LH值均较对照组明显降低。
1.5无精子症患者Y染色体微缺失发病率为7.94%(55/693)。缺失最易发生的趋势为AZFc区。最易缺失的位点为SY152、SY255和SY254。家系研究显示Y染色体微缺失大部分为新发突变,仅有少数病例遗传自父亲。
1.6和对照组相比,AZFc区缺失患者的睾丸体积减小,果糖和α糖苷酶水平升高。此外,AZFc、AZFb+c和AZFb区缺失患者抑制素B水平明显低于对照组。
1.7和对照组相比,AZFc、AZFb和AZFb+c区缺失患者FSH高：AZFc、 AZFb区缺失患者PRL高；AZFc区缺失患者LH水平高,而AZFc、AZFb和AZFb+c区缺失患者T和T/LH水平低。
2.精液质量差患者相关结果
2.1中国东北精液质量差患者中,核型异常比例为12.01%(83/691)。其中,KS最为常见(4.49%),其次为染色体多态性(3.76%)和易位(3.18%)。
2.2KS和易位携带者的睾丸体积明显小于对照组,而多态患者睾丸体积和对照组相比没有明显差异。
2.3和对照组相比,KS患者的FSH和LH水平显著升高,而在多态患者中,仅FSH水平显著升高。此外,所有精液质量差的异常核型患者T和T/LH值均低于对照组。
2.4精液质量差的非嵌合KS患者表现为少精子症和隐匿精子症。与对照组相比,这些患者睾丸体积小、FSH和LH水平升高、T和T/LH值降低。
2.5精液质量差患者中,Y染色体缺失率为5.50%。其中,AZFc区缺失率最高。最易缺失的位点仍为SY152、SY255和SY254。家系研究显示所有的Y染色体微缺失都是新生突变而来。
2.6与对照组和Y染色体未缺失组相比,精液质量差患者的Y染色体微缺失患者睾丸体积小,T/LH值低,FSH和LH水平高。
3.无精子症患者与精液质量差患者比较
3.1无精子症患者的核型异常比率显著高于精液质量差的患者,而二者Y染色体微缺失发生率无明显差异。
3.2无精子症患者(包括遗传因素和非遗传因素所致无精)的年龄和睾丸体积均比精液质量异常患者显著减小。
3.3遗传因素所致无精子症患者的α-糖苷酶水平比精液质量差患者低,而抑制素B和果糖水平无明显差异。
3.4和精液质量差患者相比,遗传和非遗传因素所致的无精子症患者FSH和LH水平均高,而PRL、T和E2水平无明显差异。
3.5和非遗传学因素所致无精子患者相比,遗传因素所致无精子患者其FSH和LH水平显著升高；T和T/LH水平显著降低,而PRL、T和E2水平无明显差异。
3.6精液质量差患者中,非遗传因素患者的年龄,睾丸体积,精浆生化,抑制素B和激素水平与遗传因素来源的患者相比均无明显差异。
结论：
1.中国东北地区无精子患者致病遗传学因素主要为克氏症和Y染色体微缺失。相比其他种类核型异常患者,克氏症患者的睾丸更小,FSH和LH水平更高,T水平更低。Y染色体微缺失的无精子症患者激素异常与克氏症患者相似。
2.中国东北精液质量差患者遗传学致病因素较为复杂,其中Y染色体微缺失是致病最主要病因。绝大部分的Y染色体缺失患者都为AZFc区缺失,且这种缺失多是新发突变而来。
3.和Y染色体微缺失相比,核型异常更容易导致无精子症发生。激素结果提示遗传因素导致的生殖激素水平的变化和生精功能障碍关系密切。
Infertility refers to couples who have not become pregnant after at least1year of unprotected intercourse. Over many years in early20th century the majority if not all of human societies believed that infertility always is a woman's problem. But nowadays there is a clear fact that male factors contributed about half of infertility cases. Regarding the possible causes of infertility, wide range of disorders ranging from genetic disorders to coital problems can influence male fertility. Among these genetic aberrations were considered as one of the most frequent and interesting causes, that contributed about30%causes of infertile male, involving both chromosomal disorders and single gene mutations.
Genetic disorders that influence male fertility including two major groups as follow:chromosomal abnormalities which characterized by abnormal karyotype, including sex chromosome abnormalities, and autosomal chromosomal abnormalities. The second type of genetic disorders is referred to Y chromosome microdeletions which characterized by azoospermia factor gene deletions. The clinical phenotype of infertile men with genetic aberrations is of wide variety, in some cases infertile men attend the reproductive clinic with completely absent of sperm in the ejaculated semen (azoospermia), other cases showed small amount of sperm in their ejaculated semen. Why infertile men with genetic aberrations have specific clinical phenotype? What's the relationship between abnormal semen quality and genetic disorders? To answer these questions, we investigated1384infertile men from Northeast of China. These patients were divided into693azoospermic patients and691patients with poor semen quality by semen analysis. Other50normal fertile men aged24-37years old were included as control. Karyotype analysis was done by using G-banding method and Y chromosome microdeletion was detected by using polymerase chain reaction assay PCR. Moreover, hormone level was tested by eleterocheiluminescence immunoassays. All the clinical and lab results were analyzed to illuminate the relationship between abnormal semen quality and genetic disorders. This study was approved by the ethics committee of the First Bethune Hospital of Jilin University.
Results:
1. Associated results of azoospermic men
1.1Abnormal karyotype among infertile azoospermic patients in Northeast China was detected at a rate of23.52%(163/693). Of these, Klinefelter syndrome (KS) is the most frequent (17.75%of the azoospermic patients), followed by Chromosome polymorphism (3.32%), and Translocation (0.72%).
1.2The volumes testis of Klinefelter syndrome and Translocation carriers were significantly smaller than those of control fertile males in azoospermic group, respectively, while no significant difference was noted in those of Polymorphic, and inversion group when compared with control.
1.3The levels of inhibin B of seminal plasmal of Polymorphic and Klinefelter syndrome azoospermic patients were significantly lower than those of control fertile males, respectively. Moreover, the level of Fructose in Translocation group was found significantly higher than those of control fertile males. No significant difference was noted in different biochemical of seminal plasma of other azoospermic abnormal karyotype patients compared with those of azoospermic of Klinefelter syndrome carners.
1.4FSH, LH and E2hormones levels of Polymorphic and Klinefelter syndrome azoospermic patients were significantly higher than those of control, respectively, while no significant difference of PRL, FSH, LH and E2levels was found between Translocation/Inversion and control group. Interesting, T hormone and T/LH ratio of all chromosomal abnormalities among azoospermic patients were significantly lower than those of control.
1.5The incidence of Y chromosome microdeletion was found at a rate of7.94%(55/693) among azoospermic patients. AZFc is most deleted region, and the most frequent deletion pattern is deletion of sY152, sY255and sY254.Additionally, most of deletions were de novo mutations, but some of cases were inherited from their fathers.
1.6The testicular volumes of AZFc azoospermic deletions patient were significantly smaller, and the levels of Fructose and a-glucosidase of AZFc deletions were significantly higher than those of control fertile males. Moreover, the levels of Inhibin B of patients with AZFc, AZFb+c, and AZFb deletions were significantly lower than those of control, respectively.
1.7FSH levels of patients with AZFc, AZFb+c, and AZFb deletions, LH level of patients with AZFc deletions and PRL level of patients with AZFc and AZFb deletions were significantly higher, while T and T/LH ratio of patients with AZFc, AZFb+c, and AZFb deletions were significantly lower than those of control.
2. Associated results of patients with poor semen quality
2.1Abnormal karyotype among patients with poor semen quality in Northeast China was detected at a rate of12.01%(83/691). Of these, Klinefelter syndrome is the most frequent (4.49%of the patients with poor semen quality), followed by Chromosome polymorphism (3.76%), and Translocation (3.18%).
2.2The volumes testis of Klinefelter syndrome and Translocation carriers were significantly smaller than those of control fertile males in poor semen quality groups, respectively, while no significant difference was noted in those of Polymorphic group compared with control.
2.3FSH and LH hormones levels of Klinefelter syndrome patients with poor semen quality were significantly higher than those of control, while in Polymorphism patients, only FSH level were significantly higher than those of control. T hormone and T/LH ratio of all chromosomal abnormalities among poor semen quality patients were significantly lower than those of control.
2.4Non-moisaic Klinefelter syndrome men with poor semen quality were all oligozoospermic and cryptozoospermic. Compared with control, all these patients showed smaller testis volume, higher FSH and LH and lower T and T/LH.
2.5The incidence of Y chromosome microdeletion was found at a rate of5.50%(38/691) among patients with poor semen quality. AZFc is most deleted region, and the most frequent deletion pattern is also deletion of sY152, sY255and sY254. All the deletions which referred in pedigree study were de novo mutation.
2.6Compared with control and without AZF deletion group, poor semen quality patients with AZF deletion showed smaller testis volume, higher FSH and LH and lower T and T/LH.
3. Comparison between azoospermic and poor-semen quality patients
3.1The incidence of abnormal karyotype among infertile azoospermic patients compared with that of poor semen quality patients is significantly higher, while the incidence of Y chromosome microdeletion was found to be not statistically different from that among poor semen quality patients.
3.2Compared with corresponding patients with poor semen quality, the age and testis volumes of all azoospermic group, including group of azoospermia with genetic factor and group of azoospermia without genetic factor, were significantly smaller.
3.3Compared with corresponding patients with poor semen quality, the levels of a-glycosidase of azoospermia, and azoospermia with genetic factor patients were significantly lower. However, there was no statistically different was noted in levels of inhibin B and Fructose.
3.4Compared with corresponding patients with poor semen quality, the levels of FSH, LH were significantly higher in all azoospermic patients of different etiology. No significant difference was noted in PRL, T and E2levels.
3.5Compared with group of azoospermia without genetic factor, the age and testis volumes were smaller, the level of Fructose, a-glucosidase, FSH and LH were higher, and the level of T and T/LH were lower in azoospermic patients with genetic factor. No significant difference was noted on inhibin B, PRL and E2levels.
3.6Compared with group of poor-semen without genetic factor, no significant difference was noted about age, testis volumes, biochemicals of seminal plasma, inhibin B and hormone levels in group of poor-semen with genetic factor.
Conclusions
1. In Northeast of China, important genetic factor of azoospermic patients were Klinefelter syndrome and Y chromosome microdeletion. Klinefelter syndrome patients suffered from smaller testis, higher FSH and LH, and lower T and T/LH than other abnormal karyotype carriers. In addition, the azoospermic patients with Y chromosome microdeletions had similar sex hormones abnormality as KS patients.
2. In Northeast of China, genetic factors of patients with poor semen quality were diverse. Y chromosome microdeletion played the most important role for causing poor semen quality. Almost all this kind of patients had gene microdeletion in the AZFc region, and these deletions were derived from de novo mutation.
3. Compared with Y chromosome microdeletion, abnormal karyotype tends to cause azoospermia. Genetic disorder may leads to azoospermia by elevated FSH, LH and low T. Moreover, the extent of dyszoospermia was closely association with the value of FSH, LH and T.
遗传因素影响男性的生育能力,包括染色体核型异常和Y染色体微缺失。遗传所致不育男性临床表型多样,有些男性射出精液中完全没有精子(无精子症),还有一些男性射出精液中仅有少量精子。为什么遗传所致的不育男性会有不同的临床表型?精液质量异常和遗传因素之间存在什么样的关系?为了回答这些问题,我们对中国东北的1384例不育男性进行了遗传因素分析。这些患者按精液常规结果分为693例无精子症患者和691例精液质量差的患者。此外,50例年龄在24-37岁之间的正常生育男性作为对照。我们通过G显带技术进行染色体核型分析,通过多重PCR技术进行Y染色体微缺失检测,通过电化学免疫荧光方法检测激素水平。最终,我们对临床和实验室结果进行分析来研究精液质量异常和遗传因素之间的关系。本研究经吉林大学白求恩第一医院伦理委员会同意。
结果：
1.无精子症患者相关结果
1.1中国东北无精子症患者中,核型异常比例为23.52%(163/693)。其中,Klinefelter综合征(KS)最为常见(17.75%),其次为染色体多态性(3.32%)和易位(0.72%)
1.2在无精子症患者中,KS和易位携带者的睾丸体积明显小于对照组,而多态和倒位患者睾丸体积和对照组相比没有明显差异。
1.3在无精子症患者中,多态和KS组精浆抑制素B水平明显低于对照组,易位组果糖水平明显高于对照组。KS患者和其他异常核型患者相比精浆生化水平无明显差异。
1.4相比于对照组,多态和KS患者FSH、LH和E2水平升高,而易位和倒位患者其PRL、FSH、LH和E2水平变化不大。值得注意的是,所有染色体异常患者其T和T/LH值均较对照组明显降低。
1.5无精子症患者Y染色体微缺失发病率为7.94%(55/693)。缺失最易发生的趋势为AZFc区。最易缺失的位点为SY152、SY255和SY254。家系研究显示Y染色体微缺失大部分为新发突变,仅有少数病例遗传自父亲。
1.6和对照组相比,AZFc区缺失患者的睾丸体积减小,果糖和α糖苷酶水平升高。此外,AZFc、AZFb+c和AZFb区缺失患者抑制素B水平明显低于对照组。
1.7和对照组相比,AZFc、AZFb和AZFb+c区缺失患者FSH高：AZFc、 AZFb区缺失患者PRL高；AZFc区缺失患者LH水平高,而AZFc、AZFb和AZFb+c区缺失患者T和T/LH水平低。
2.精液质量差患者相关结果
2.1中国东北精液质量差患者中,核型异常比例为12.01%(83/691)。其中,KS最为常见(4.49%),其次为染色体多态性(3.76%)和易位(3.18%)。
2.2KS和易位携带者的睾丸体积明显小于对照组,而多态患者睾丸体积和对照组相比没有明显差异。
2.3和对照组相比,KS患者的FSH和LH水平显著升高,而在多态患者中,仅FSH水平显著升高。此外,所有精液质量差的异常核型患者T和T/LH值均低于对照组。
2.4精液质量差的非嵌合KS患者表现为少精子症和隐匿精子症。与对照组相比,这些患者睾丸体积小、FSH和LH水平升高、T和T/LH值降低。
2.5精液质量差患者中,Y染色体缺失率为5.50%。其中,AZFc区缺失率最高。最易缺失的位点仍为SY152、SY255和SY254。家系研究显示所有的Y染色体微缺失都是新生突变而来。
2.6与对照组和Y染色体未缺失组相比,精液质量差患者的Y染色体微缺失患者睾丸体积小,T/LH值低,FSH和LH水平高。
3.无精子症患者与精液质量差患者比较
3.1无精子症患者的核型异常比率显著高于精液质量差的患者,而二者Y染色体微缺失发生率无明显差异。
3.2无精子症患者(包括遗传因素和非遗传因素所致无精)的年龄和睾丸体积均比精液质量异常患者显著减小。
3.3遗传因素所致无精子症患者的α-糖苷酶水平比精液质量差患者低,而抑制素B和果糖水平无明显差异。
3.4和精液质量差患者相比,遗传和非遗传因素所致的无精子症患者FSH和LH水平均高,而PRL、T和E2水平无明显差异。
3.5和非遗传学因素所致无精子患者相比,遗传因素所致无精子患者其FSH和LH水平显著升高；T和T/LH水平显著降低,而PRL、T和E2水平无明显差异。
3.6精液质量差患者中,非遗传因素患者的年龄,睾丸体积,精浆生化,抑制素B和激素水平与遗传因素来源的患者相比均无明显差异。
结论：
1.中国东北地区无精子患者致病遗传学因素主要为克氏症和Y染色体微缺失。相比其他种类核型异常患者,克氏症患者的睾丸更小,FSH和LH水平更高,T水平更低。Y染色体微缺失的无精子症患者激素异常与克氏症患者相似。
2.中国东北精液质量差患者遗传学致病因素较为复杂,其中Y染色体微缺失是致病最主要病因。绝大部分的Y染色体缺失患者都为AZFc区缺失,且这种缺失多是新发突变而来。
3.和Y染色体微缺失相比,核型异常更容易导致无精子症发生。激素结果提示遗传因素导致的生殖激素水平的变化和生精功能障碍关系密切。
Infertility refers to couples who have not become pregnant after at least1year of unprotected intercourse. Over many years in early20th century the majority if not all of human societies believed that infertility always is a woman's problem. But nowadays there is a clear fact that male factors contributed about half of infertility cases. Regarding the possible causes of infertility, wide range of disorders ranging from genetic disorders to coital problems can influence male fertility. Among these genetic aberrations were considered as one of the most frequent and interesting causes, that contributed about30%causes of infertile male, involving both chromosomal disorders and single gene mutations.
Genetic disorders that influence male fertility including two major groups as follow:chromosomal abnormalities which characterized by abnormal karyotype, including sex chromosome abnormalities, and autosomal chromosomal abnormalities. The second type of genetic disorders is referred to Y chromosome microdeletions which characterized by azoospermia factor gene deletions. The clinical phenotype of infertile men with genetic aberrations is of wide variety, in some cases infertile men attend the reproductive clinic with completely absent of sperm in the ejaculated semen (azoospermia), other cases showed small amount of sperm in their ejaculated semen. Why infertile men with genetic aberrations have specific clinical phenotype? What's the relationship between abnormal semen quality and genetic disorders? To answer these questions, we investigated1384infertile men from Northeast of China. These patients were divided into693azoospermic patients and691patients with poor semen quality by semen analysis. Other50normal fertile men aged24-37years old were included as control. Karyotype analysis was done by using G-banding method and Y chromosome microdeletion was detected by using polymerase chain reaction assay PCR. Moreover, hormone level was tested by eleterocheiluminescence immunoassays. All the clinical and lab results were analyzed to illuminate the relationship between abnormal semen quality and genetic disorders. This study was approved by the ethics committee of the First Bethune Hospital of Jilin University.
Results:
1. Associated results of azoospermic men
1.1Abnormal karyotype among infertile azoospermic patients in Northeast China was detected at a rate of23.52%(163/693). Of these, Klinefelter syndrome (KS) is the most frequent (17.75%of the azoospermic patients), followed by Chromosome polymorphism (3.32%), and Translocation (0.72%).
1.2The volumes testis of Klinefelter syndrome and Translocation carriers were significantly smaller than those of control fertile males in azoospermic group, respectively, while no significant difference was noted in those of Polymorphic, and inversion group when compared with control.
1.3The levels of inhibin B of seminal plasmal of Polymorphic and Klinefelter syndrome azoospermic patients were significantly lower than those of control fertile males, respectively. Moreover, the level of Fructose in Translocation group was found significantly higher than those of control fertile males. No significant difference was noted in different biochemical of seminal plasma of other azoospermic abnormal karyotype patients compared with those of azoospermic of Klinefelter syndrome carners.
1.4FSH, LH and E2hormones levels of Polymorphic and Klinefelter syndrome azoospermic patients were significantly higher than those of control, respectively, while no significant difference of PRL, FSH, LH and E2levels was found between Translocation/Inversion and control group. Interesting, T hormone and T/LH ratio of all chromosomal abnormalities among azoospermic patients were significantly lower than those of control.
1.5The incidence of Y chromosome microdeletion was found at a rate of7.94%(55/693) among azoospermic patients. AZFc is most deleted region, and the most frequent deletion pattern is deletion of sY152, sY255and sY254.Additionally, most of deletions were de novo mutations, but some of cases were inherited from their fathers.
1.6The testicular volumes of AZFc azoospermic deletions patient were significantly smaller, and the levels of Fructose and a-glucosidase of AZFc deletions were significantly higher than those of control fertile males. Moreover, the levels of Inhibin B of patients with AZFc, AZFb+c, and AZFb deletions were significantly lower than those of control, respectively.
1.7FSH levels of patients with AZFc, AZFb+c, and AZFb deletions, LH level of patients with AZFc deletions and PRL level of patients with AZFc and AZFb deletions were significantly higher, while T and T/LH ratio of patients with AZFc, AZFb+c, and AZFb deletions were significantly lower than those of control.
2. Associated results of patients with poor semen quality
2.1Abnormal karyotype among patients with poor semen quality in Northeast China was detected at a rate of12.01%(83/691). Of these, Klinefelter syndrome is the most frequent (4.49%of the patients with poor semen quality), followed by Chromosome polymorphism (3.76%), and Translocation (3.18%).
2.2The volumes testis of Klinefelter syndrome and Translocation carriers were significantly smaller than those of control fertile males in poor semen quality groups, respectively, while no significant difference was noted in those of Polymorphic group compared with control.
2.3FSH and LH hormones levels of Klinefelter syndrome patients with poor semen quality were significantly higher than those of control, while in Polymorphism patients, only FSH level were significantly higher than those of control. T hormone and T/LH ratio of all chromosomal abnormalities among poor semen quality patients were significantly lower than those of control.
2.4Non-moisaic Klinefelter syndrome men with poor semen quality were all oligozoospermic and cryptozoospermic. Compared with control, all these patients showed smaller testis volume, higher FSH and LH and lower T and T/LH.
2.5The incidence of Y chromosome microdeletion was found at a rate of5.50%(38/691) among patients with poor semen quality. AZFc is most deleted region, and the most frequent deletion pattern is also deletion of sY152, sY255and sY254. All the deletions which referred in pedigree study were de novo mutation.
2.6Compared with control and without AZF deletion group, poor semen quality patients with AZF deletion showed smaller testis volume, higher FSH and LH and lower T and T/LH.
3. Comparison between azoospermic and poor-semen quality patients
3.1The incidence of abnormal karyotype among infertile azoospermic patients compared with that of poor semen quality patients is significantly higher, while the incidence of Y chromosome microdeletion was found to be not statistically different from that among poor semen quality patients.
3.2Compared with corresponding patients with poor semen quality, the age and testis volumes of all azoospermic group, including group of azoospermia with genetic factor and group of azoospermia without genetic factor, were significantly smaller.
3.3Compared with corresponding patients with poor semen quality, the levels of a-glycosidase of azoospermia, and azoospermia with genetic factor patients were significantly lower. However, there was no statistically different was noted in levels of inhibin B and Fructose.
3.4Compared with corresponding patients with poor semen quality, the levels of FSH, LH were significantly higher in all azoospermic patients of different etiology. No significant difference was noted in PRL, T and E2levels.
3.5Compared with group of azoospermia without genetic factor, the age and testis volumes were smaller, the level of Fructose, a-glucosidase, FSH and LH were higher, and the level of T and T/LH were lower in azoospermic patients with genetic factor. No significant difference was noted on inhibin B, PRL and E2levels.
3.6Compared with group of poor-semen without genetic factor, no significant difference was noted about age, testis volumes, biochemicals of seminal plasma, inhibin B and hormone levels in group of poor-semen with genetic factor.
Conclusions
1. In Northeast of China, important genetic factor of azoospermic patients were Klinefelter syndrome and Y chromosome microdeletion. Klinefelter syndrome patients suffered from smaller testis, higher FSH and LH, and lower T and T/LH than other abnormal karyotype carriers. In addition, the azoospermic patients with Y chromosome microdeletions had similar sex hormones abnormality as KS patients.
2. In Northeast of China, genetic factors of patients with poor semen quality were diverse. Y chromosome microdeletion played the most important role for causing poor semen quality. Almost all this kind of patients had gene microdeletion in the AZFc region, and these deletions were derived from de novo mutation.
3. Compared with Y chromosome microdeletion, abnormal karyotype tends to cause azoospermia. Genetic disorder may leads to azoospermia by elevated FSH, LH and low T. Moreover, the extent of dyszoospermia was closely association with the value of FSH, LH and T.
引文
[1]Gnoth C, Godehardt E, Frank-Herrmann P, Friol K, Tigges J, Freundl G. Definition and prevalence of subfertility and infertility. Hum Reprod.2005 May;20(5):1144-7.
[2]De Kretser DM and Baker HWG. Infertility in men: recent advances and continuing controversies. J Clin Endocrinol Metab.1999; 84:3443-3450.
[3]Ferlin A, Arredi B, Foresta C. Genetic causes of male infertility. Reprod Toxicol.2006 Aug;22(2):133-41.
[4]O'Flynn O'Brien KL, Varghese AC, Agarwal A. The genetic causes of male factor infertility:a review. Fertil Steril.2010 Jan;93(1):1-12.
[5]Cooper TG, Noonan E, Von Eckardstein S, Auger J, Baker HWG, Behre HM, Haugen TB, Kruger T, Wang C. World Health Organization reference values for human semen characteristics. Human Reproduction Update.2009; 16 (3): 231-5.
[6]Hargreave TB, McGowan B, Harvey J, McParland M, Elton RA. Is a male infertility clinic of any use?. Br. J. Urol.1986 April; 58 (2):188-93.
[7]Hwang K, Walters RC, Lipshultz LI. Contemporary concepts in the evaluation and management of male infertility. Nat. Rev. Urol.2011 February; 8 (2):86-94.
[8]Roze C, Touraine P, Leger J, de Roux N. Congenital hypogonadotropic hypogonadism. Ann Endocrinol (Paris).2009 Mar;70(1):2-13.
[9]Nilsson LA, Roepstorff C, Kiens B, Billig H, Ling C. Prolactin suppresses malonyl-CoA concentration in human adipose tissue. Horm Metab Res.2009 Oct;41(10):747-51.
[10]Reisch N, Flade L, Scherr M, Rottenkolber M, Pedrosa Gil F, Bidlingmaier M, Wolff H, Schwarz HP, Quinkler M, Beuschlein F, Reincke M. High prevalence of reduced fecundity in men with congenital adrenal hyperplasia. J Clin Endocrinol Metab.2009 May;94(5):1665-70.
[11]Devoto C E, Madariaga A M, Fernandez W. Congenital adrenal hyperplasia causing male infertility. Report of one case.Rev Med Chil.2011 Aug; 139(8):1060-5.
[12]Budzynska E, Ben-Skowronek I. Testicular adrenal rest tumours in boys with congenital adrenal hyperplasia:case report and literature review. Pediatr Endocrinol Diabetes Metab.2011;17(4):239-42.
[13]Nikoobakht MR, Aloosh M, Nikoobakht N, Mehrsay AR, Biniaz F, Karjalian MA. The role of hypothyroidism in male infertility and erectile dysfunction. Urol J.2012 Winter;9(1):405-9.
[14]Purvis K, Christiansen E. Infection of the male reproductive tract. Impact, diagnosis and treatment in relation to male infertility. Int J Androl.1993:16:1-13.
[15]Goluboff ET, Stifelman MD, Fisch H. Ejaculatory duct obstruction in infertile men. Urology.1995:45:925-931.
[16]Di Carlo A. Sexually transmitted diseases syndromic approach:urethral discharge. G Ital Dermatol Venereol.2012 Aug;147(4):389-94.
[17]Belmonte IG, Martin de Serrano MN. Partial obstruction of the seminal path, a frequent cause of oligozoospermia in men. Hum Reprod.1998:13:3402-3405.
[18]Li H, Wen Q, Li H, Zhao L, Zhang X, Wang J, Cheng L, Yang J, Chen S, Ma X, Wang B. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) in Chinese patients with congenital bilateral absence of vas deferens. J Cyst Fibros.2012 Jul;11(4):316-23.
[19]Pollack AE, et al. (2007). Female and male sterilization. In RA Hatcher et al., eds., Contraceptive Technology,19th ed., pp.361-401. New York:Ardent Media.
[20]Labrecque M, Nazerali H, Mondor M, Fortin V, Nasution M. Effectiveness and complications associated with 2 vasectomy occlusion techniques. J Urol. 2002 Dec; 168(6):2495-8
[21]Fode M, Krogh-Jespersen S, Brackett NL, Ohl DA, Lynne CM, S(?)nksen J. Male sexual dysfunction and infertility associated with neurological disorders. Asian J Androl.2012 Jan;14(1):61-8.
[22]Isidro ML. Sexual dysfunction in men with type 2 diabetes. Postgrad Med J. 2012 Mar;88(1037):152-9.
[23]Aust TR, Lewis-Jones DI. Retrograde ejaculation and male infertility. Hosp Med.2004 Jun;65(6):361-4.
[24]Amano T, Imao T, Takemae K, Yamauchi K. Ejaculatory disorder caused by doxazosin administration for blood pressure control in patient with pheo-chomocytoma. Hinyokika Kiyo.2009 Jun;55(6):377-80.
[25]Rowland D, McMahon CG, Abdo C, Chen J, Jannini E, Waldinger MD, Ahn TY. Disorders of orgasm and ejaculation in men. J Sex Med.2010 Apr;7(4 Pt 2):1668-86.
[26]Kolon FT, Patel PR, Huff SD. Cryptorchidism:diagnosis, treatment and long-term prognosis. Urol Clin North Am.2004;31:469-80.
[27]Hadziselimovic F, Herzog B. The importance of both and early orchidopexy and germ cell maturation for fertility. Lancet.2001;358:1156-7.
[28]Pereira JR, Neves S, Leite F, Baptista C, Santos E, Ferrao A, Figueiredo C. Cryptorchidism in adolescence. Acta Med Port.2011 Dec;24 Suppl 3:715-8.
[29]La Vignera S, Calogero AE, Condorelli R, Marziani A, Cannizzaro MA, Lanzafame F, Vicari E. Cryptorchidism and its long-term complications. Eur Rev Med Pharmacol Sci.2009 Sep-Oct;13(5):351-6.
[30]Agoulnik AI, Huang Z, Ferguson L. Spermatogenesis in cryptorchidism. Methods Mol Biol.2012;825:127-47.
[31]Pellati D, Mylonakis I, Bertoloni G, Fiore C, Andrisani A, Ambrosini G, Armanini D. Genital tract infections and infertility. Eur J Obstet Gynecol Reprod Biol.2008 Sep;140(1):3-1l.
[32]Hofny ER, Ali ME, Taha EA, Nafeh HM, Sayed DS, Abdel-Azeem HG, Abdou EF, Kamal GM, Mostafa T. Semen and hormonal parameters in men with chronic hepatitis C infection. Fertil Steril.2011 Jun 30;95(8):2557-9.
[33]Chen JW, Cui Y, Zhang XX. Investigate the impact of hepatitis B virus infection on sperm DNA integrity. Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi.2011 Oct;25(5):345-7.
[34]Baker BW, Surratt JK, Run W. Missed testicular torsion presenting with male infertility and erectile dysfunction. Zhonghua Nan Ke Xue.2005 Aug;11(8):615-6.
[35]Mongiat-Artus P. Torsion of the spermatic cord and testicular annexes. Ann Urol (Paris).2004 Feb;38(1):25-34.
[36]Filho DW, Torres MA, Bordin AL, Crezcynski-Pasa TB, Boveris A. Spermatic cord torsion, reactive oxygen and nitrogen species and ischemia-reperfusion injury. Mol Aspects Med.2004 Feb-Apr;25(1-2):199-210.
[37]Dokmeci D. Testicular torsion, oxidative stress and the role of antioxidant therapy. Folia Med (Plovdiv).2006;48(3-4):16-21.
[38]Zilberman D, Inbar Y, Heyman Z, Shinhar D, Bilik R, Avigad I, Jonas P, Ramon J, Mor Y.Torsion of the cryptorchid testis--can it be salvaged? J Urol.2006 Jun;175(6):2287-9.
[39]Aning J, Gillatt D. When should patients with varicocoele be referred? Practitioner.2012 Apr;256(1750):17-20,2-3.
[40]Kroese AC, de Lange NM, Collins J, Evers JL. Surgery or embolization for varicoceles in subfertile men. Cochrane Database Syst Rev.2012 Oct 17;10:CD000479.
[41]Guo SJ, Sun ZJ, Li W. New insights about the early diagnosis of fertility impairment in varicoceles:the DNA repair gene example. Med Hypotheses. 2012Apr;78(4):536-8.
[42]Keene DJ, Sajad Y, Rakoczy G, Cervellione RM.Testicular volume and semen parameters in patients aged 12 to 17 years with idiopathic varicocele. J Pediatr Surg.2012 Feb;47(2):383-5.
[43]Calogero A, Polosa R, Perdichizzi A, Guarino F, La Vignera S, Scarfia A, Fratantonio E, Condorelli R, Bonanno O, Barone N, Burrello N, D'Agata R, Vicari E. Cigarette smoke extract immobilizes human spermatozoa and induces sperm apoptosis. Reprod Biomed Online.2009 Oct; 19(4):564-71.
[44]Sepaniak S, Forges T, Monnier-Barbarino P. Cigarette smoking and fertility in women and men.Gynecol Obstet Fertil.2006 Oct;34(10):945-9.
[45]Sermondade N, Elloumi H, Berthaut I, Mathieu E, Delarouziere V, Ravel C, Mandelbaum J. Progressive alcohol-induced sperm alterations leading to spermatogenic arrest, which was reversed after alcohol withdrawal. Reprod Biomed Online.2010 Mar;20(3):324-7.
[46]Mathur PP, D' Cruz SC. The effect of environmental contaminants on testicular function. Asian J Androl.2011 Jul;13(4):585-91.
[47]Wong EW, Cheng CY. Impacts of environmental toxicants on male reproductive dysfunction. Trends Pharmacol Sci.2011 May;32(5):290-9.
[48]Pacey AA. Environmental and lifestyle factors associated with sperm DNA damage. Hum Fertil (Camb).2010 Dec; 13(4):189-93.
[49]Bonde, J.P. (1996) Environmental Factors. In Comhaire, F.H. (ed.), Male Infertility, Clinical Investigation, Cause Evaluation and Treatment. Chapman and Hall, London, pp.267-284.
[50]Spira, A. and Multigner, L. (1998). The effect of industrial and agricultural pollution on human spermatogenesis. Hum. Reprod.,13,2041-2042.
[51]Singh DK, Hersey K, Perlis N, Crook J, Jarvi K, Fleshner N. The effect of radiation on semen quality and fertility in men treated with brachytherapy for early stage prostate cancer. J Urol.2012 Mar;187(3):987-9.
[52]P Thonneau, L Bujan, L Multigner and R Mieusset. Occupational heat exposure and male fertility:a review. Human Reproduction Volume 13, Issue 8Pp.2122-2125.
[53]Dada R, Kumar R, Shamsi MB, Kumar R, Kucheria K, Sharma RK, et al. Higher frequency of Yq microdeletions in sperm DNA as compared to DNA isolated from blood. Asian J Androl.2007;9:720-2.
[54]Yoshida A, Miura K, Shirai M. Cytogenetic survey of 1,007 males. Urol Int. 1997;58:166-76
[55]Hassold T, Hunt P. To err (meiotically) is human: the genesis of human aneuploidy. Nat Rev Genet 2001; 2:280-91.
[56]C. Foresta, A. Ferlin, L. Gianaroli, B. DallapiccolaGuidelines for the appropriate use of genetic tests in infertile couples. Eur J Hum Genet,10 (2002), pp.303-312.
[57]C. Foresta, A. Garolla, L. Bartoloni, A. Bettella, A. Ferlin. Genetic abnormalities among severely oligospermic men who are candidates for intracytoplasmic sperm injection. J Clin Endocrinol Metab,90 (2005), pp. 152-156.
[58]C. Foresta, C. Galeazzi, A. Bettella, M. Stella, C. Scandellari. High incidence of sperm sex chromosomes aneuploidies in two patients with Klinefelter's syndrome.
[59]C.Foresta, A. Ferlin, L. Gianaroli, B. Dallapiccola. Guidelines for the appropriate use of genetic tests in infertile couples. Eur J Hum Genet,10 (2002), pp.303-312.
[60]Pina-Neto JM, Carrara RC, Bisinella R, Mazzucatto LF, Martins MD, Sartoratto E, Yamasaki R. Somatic cytogenetic and azoospermia factor gene microdeletion studies in infertile men. Braz J Med Biol Res.2006 Apr;39(4):555-61.
[61]Groth KA, Skakkebaek A, Host C, Gravholt CH, Bojesen A. Klinefelter Syndrome--A Clinical Update.J Clin Endocrinol Metab.2012 Nov 1.
[62]Balkan M, Tekes S, Gedik A. Cytogenetic and Y chromosome microdeletion screening studies in infertile males with Oligozoospermia and Azoospermia in Southeast Turkey. J Assist Reprod Genet 2008 Nov-Dec;25(11-12):559-65.
[63]Garcia-Quevedo L, Blanco J, Sarrate Z, Catala V, Bassas L, Vidal F. Hidden mosaicism in patients with Klinefelter's syndrome:implications for genetic reproductive counselling. Hum Reprod 2011;26(12):3486-93.
[64]Tincani BJ, Mascagni BR, Pinto RD, Guaragna-Filho G, Castro CC, Sewaybricker LE, Viguetti-Campos NL, Marques-de-Faria AP, Maciel-Guerra AT, Guerra-Junior G. Klinefelter syndrome: an unusual diagnosis in pediatric patients. J Pediatr (Rio J).2012 Jul;88(4):323-7.
[65]Messina MF,Sgro DL, Aversa T,Pecoraro M, Valenzise M,De Luca F.A characteristic cognitive and behavioral pattern as a clue to suspect Klinefelter syndrome in prepubertal age. J Am Board Fam Med.2012 Sep-Oct;25(5):745-9.
[66]Zhao LM, Jiang H, Hong K, Huang J, Tang WH, Mao JM, Qiao J, Liu P, Lian Y, Ma LL. Successful microdissection testicular sperm extraction in patients with nonmosaic Klinefelter syndrome:three cases report. Beijing Da Xue Xue Bao 2012;44(4):547-50.
[67]Selice R,Di Mambro A,Garolla A,Ficarra V,Iafrate M,Ferlin A,Foresta C.Spermatogenesis in Klinefelter syndrome. J Endocrinol Invest 2010; 33(1l):789-93.
[68]Van Saen D, Gies I, De Schepper J, Tournaye H, Goossens E. Can pubertal boys with Klinefelter syndrome benefit from spermatogonial stem cell banking?. Hum Reprod 2012; 27(2):323-30.
[69]Oates R:The natural history of endocrine function and spermatogenesis in Klinefelter syndrome:what the data show. Fertil Steril 2012 Aug;98(2):266-73.
[70]A. Ferlin, A. Garolla, C. Foresta. Chromosome abnormalities in sperm of individuals with constitutional sex chromosomal abnormalities. Cytogenet Genome Res,111 (2005), pp.310-316.
[71]B.E. Reubinoff, D. Abeliovich, M. Werner, J.G. Schenker, A. Safran, A. Lewin. A birth in non-mosaic Klinefelter's syndrome after testicular fine needle aspiration, intracytoplasmic sperm injection and preimplantation genetic diagnosis. Hum Reprod,13 (1998), pp.1887-1892.
[72]R. Ron-El, D. Strassburger, S. Gelman-Kohan, S. Friedler, A. Raziel, Z. Appelman. A 47,XXY fetus conceived after ICSI of spermatozoa from a patient with non-mosaic Klinefelter's syndrome:case report. Hum Reprod,15 (2000), pp.1804-1806.
[73][73] Yatsenko AN, Yatsenko SA, Weedin JW, Lawrence AE, Patel A, Peacock S, Matzuk MM, Lamb DJ, Cheung SW, Lipshultz LI. Comprehensive 5-year study of cytogenetic aberrations in 668 infertile men. J Urol.2010 Apr; 183(4):1636-42.
[74]Rappold GA. The pseudoautosomal regions of the human sex chromosomes. Hum Genet.1993 Oct;92(4):315-24.
[75]Ferguson-Smith MA. X-Y chromosomal interchange in the aetiology of true hermaphroditism and of XX Klinefelter's syndrome. Lancet.1966 Aug 27;2(7461):475-6.
[76]Weil D, Wang I, Dietrich A, Poustka A, Weissenbach J, Petit C.Highly homologous loci on the X and Y chromosomes are hot-spots for ectopic recombinations leading to XX maleness. Nat Genet.19.
[77]Dada R, Ahmed ME, Talwar R, Kucheria K. Clinical and Genetic study in a XX (SRY negative) male. Int J Med.2002.
[78]Martin RH. Cytogenetic determinants of male fertility. Hum Reprod. Update 2008 Jul-Aug;14(4):379-90.
[79]Ross JL, Roeltgen DP, Kushner H, Zinn AR, Reiss A, Bardsley MZ, McCauley E, Tartaglia N. Behavioral and social phenotypes in boys with 47,XYY syndrome or 47,XXY Klinefelter syndrome. Pediatrics.2012 Apr;129(4):769-78.
[80]C. Alves, F. Carvalho, N. Cremades, M. Sousa, A. Barros:Unique [Y;13] translocation in a male with oligozoospermia:cytogenetic and molecular studies. Eur J Hum Genet,10 (2002), pp.467-474.
[81]P.H. Vogt, A. Edelmann, P. Hirschmann, M.R. Kohler. The azoospermia factor [AZF] of the human Y chromosome in Yq11:function and analysis in spermatogenesis. Reprod Fertil Dev,7 (1995), pp.685-693.
[82]Yumura Y, Murase M, Katayama K, Segino M, Aizawa Y, Kuroda SN, Noguchi K. Y-autosome translocation associated with male infertility: a case report; Hinyokika Kiyo.2012 Jun;58(6):307-10.
[83]Kumar R, Shamsi MB, Gaznavi MI, Jena M, Kucheria K, Kumar R, et al. Structural chromosomal anomalies and their association with reproductive failure. Obstet Gynecol Today.2007; 12:152-4.
[84]Hamerton JL, Canning N, Ray M, Smith S. A cytogenetic survey of 14,069 newborn infants:incidence of chromosomal abnormalities. Clin Genet. 1975;8:223-43.
[85]E. Therman, M. Susman. Human chromosome:structure, behaviour and effects:Springer-Verlag, New York (1993) pp.273-287.
[86]86] Huang J, Lian Y, Qiao J, Liu P. Clinical characteristics and preimplantation genetic diagnosis for male Robertsonian translocations. Beijing Da Xue Xue Bao 2012 Aug 18;44(4):544-6.
[87]Meza-Espinoza JP, Anguiano LO, Rivera H. Chromosomal abnormalities in couples with reproductive disorders. Gynecol Obstet Invest.2008;66:237-40.
[88]M. De Braekeleer, T.N. Dao. Cytogenetic studies in male infertility:a review; Hum Reprod,6 (1991), pp.245-250.
[89]Gary L Harton and Helen G Tempest. Chromosomal disorders and male infertility Asian Journal of Andrology (2012) 14,32-39.
[90]Feuk L, MacDonald J. R, Tang T, Carson A. R, Li M, et al. (2005) Discovery of human inversion polymorphisms by comparative analysis of human and chimpanzee DNA sequence assemblies. PLoS Genet 1:e56.
[91]Daniel A, Hook EB, Wulf G. Risks of unbalanced progeny at amniocentesis to carriers of chromosome rearrangements:data from United States and Canadian laboratories. Am J Med Genet.1989;31:14-53.
[92]Shah K, Sivapalan G, Gibbons N, Tempest H, Griffin DK. The genetic basis of infertility. Reproduction 2003; 126:13-25
[93]Coyne J. A, Aulard S, Berry A (1991) Lack of underdominance in a naturally-occurring pericentric inversion in Drosophila melanogaster and its implications for chromosome evolution. Genetics 129:791-802.
[94]Cortes-Gutierrez EI, Cerda-Flores RM, Davila-Rodriguez MI, Hernandez-Herrera R, Vargas-Villarreal J, Leal-Garza CH. Chromosomal abnormalities and polymorphisms in Mexican infertile men. Arch Androl 2004 Jul-Aug;50(4):261-5.
[95]Sato H, Miyamoto T, Yogev L, et al. Polymorphic alleles of the human MEI1 gene are associated with human azoospermia by meiotic arrest. Journal of Human Genetics.2006;51(6):533-540.
[96]Miyamoto T, Tsujimura A, Miyagawa Y, et al. Single nucleotide 4 polymorphism in the UBR2 gene may be a genetic risk factor for Japanese patients with azoospermia by meiotic arrest. Journal of Assisted Reproduction and Genetics.2011;28(8):743-746.
[97]Miyakawa H, Miyamoto T, Koh E, et al. Single-nucleotide polymorphisms in the SEPTIN12 gene may be a genetic risk factor for Japanese patients with sertoli cell-only syndrome. Journal of Andrology. In press.
[98]Qin Y, Xia Y, Wu W, Han X, Lu C, Ji G, Chen D, Wang H, Song L, Wang S, Wang X. Genetic variants in microRNA biogenesis pathway genes are associated with semen quality in a Han-Chinese population. Reprod Biomed Online.2012 Apr;24(4):454-61.
[99]Blennow E, Bui T, Kristofferson U, Vujic M, Annerens G, Holmberg F, Nordenskjold M. Swedish survey on extra structurally abnormal chromosomes in 39105 consecutive prenatal diagnoses:prevalence and characterization by fluorescence in situ hybridization. Prenat Diagn 1994.141019-1028.1028.
[100]Warburton U. De novo balanced chromosome rearrangements and extra marker chromosomes identified at prenatal diagnosis:clinical significance and distribution of breakpoints. Am J Hum Genet 1991.49(5)995-1013.1013.
[101]Crolla J. FISH and molecular studies of autosomal supernumerary marker chromosomes excluding those derived from chromosome 15:II. Review of the literature. Am Med Genet 1998.75367-381.381.
[102]Carrasco J J L, Otewro G A, Vilar M M C, Garcia M J L, Troyano L J M, Lopez R C C, Parache H J. Small marker chromosomes in a series of 1000 prenatal diagnoses by amniocentesis. Ann Gene 1990.3340-42.42.
[103]Sachs E S, Van Hemel J O, Den Hollander J C, Jahoda M G. Marker chromosomes in a series of 10,000 prenatal diagnoses:cytogenetic and follow-up studies. Prena Diagn 1987.781-89.89.
[104]Steinbach P, Djalali M, Hansmann I, Kattner F, Meisel-Stosiek M, Probeck H D, Schmidt A, Wolf M. The genetic significance of bisatellited marker chromosomes. Hum Genet 1983.65155-164.164.
[105]Tiepolo L, Zuffardi O. Localization of factors controlling spermatogenesis in the nonfluorescent portion of the human Y chromosome long arm. Hum Genet 1976:34:119-124.
[106]Kim MJ, Choi HW, Park SY, Song IO, Seo JT, Lee HS. Molecular and cytogenetic studies of 101 infertile men with microdeletions of Y chromosome in 1,306 infertile Korean men. J Assist Reprod Genet.2012 June:29(6):539-46.
[107]Ristanovic M, Bunjevacki V, Tulic C, Novakovic I, Perovic V, Lukovic LJ, Milasin J. Prevalence of Y chromosome microdeletions in infertile men with severe oligozoospermia in Serbia. Genet Couns.2007;18(3):337-42.
[108]Mirfakhraie R, Mirzajani F, Kalantar SM, Montazeri M, Salsabili N, Pourmand GR, Houshmand M. High prevalence of AZFb microdeletion in Iranian patients with idiopathic non-obstructive azoospermia. Indian J Med Res.2010 Sep;132:265-70.
[109]Fu J, Li L, Lu G. Relationship between microdeletion on Y chromosome and patients with idiopathic azoospermia and severe oligozoospermia in the Chinese.China Med J (Engl).2002 Jan; 115(1):72-5.
[110]Li HG, Ding XF, Zhao JX, Zuo MD, Xiong CL. Y chromosome microdeletions of 664 Chinese men with azoospermia or severe oligozoospermia. Zhonghua Yi Xue Yi Chuan Xue Za Zhi.2008 Jun;25(3):252-5.
[111]Liu YF, Ou JP, Zhou CQ, Wang Q, Wang ZL. Screening for the microdeletions of azoospermia factor on the Y chromosome in male infertile patients from Guangzhou. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2007 Oct;24(5):564-6.
[112]Zhu YJ, Liu SY, Wang H, Wei P, Ding XP. The prevalence of azoospermia factor microdeletion on the Y chromosome of Chinese infertile men detected by multi-analyte suspension array technology. Asian Androl.2008 Nov;10(6):873-81.
[113]Vogt PH, Edelmann A, Kirsch S, Henegariu O, Hirschmann P, Kiesewetter F, Kohn FM, Schill WB, Farah S, Ramos C, Hartmann M, Hartschuh W, Meschede D, Behre HM, Castel A, Nieschlag E, Weidner W, Grone HJ, Jung A, Engel W, Haidl G. Human Y chromosome azoospermia factors (AZF) mapped to different subregions in Yqll.Hum Mol Genet.1996 Ju1;5(7):933-43.
[114]Kent-First M,Muallem A, et al:Defining regions of the Y-chromosome responsible for male infertility and identification of a fourth AZF region (AZFd) by Y-chromosome microdeletion detection. Mol Reprod 1999:53:27-41.
[115]Sargent CA, Boucher CA, Kirsch S, Brown G, Weiss B, Trundley A, Burgoyne P, Saut N. Durand C, Levy N, Terriou P, Hargreave T, Cooke H, Mitchell M, Rappold GA, Affara NA. The critical region of overlap defining the AZFa male infertility interval of proximal Yq contains three transcribed sequences. J Med Genet1999;36:670-7.
[116]Lahn BT, Page DC. Functional coherence of the human Y chromosome. Sciencel997;278:675-80.
[117]Rolf C, Gromoll J, Simoni M, Nieschlag E. Natural transmission of a partial AZFb deletion of the Y chromosome over three generations:case report. Hum Reprod.2002 Sep;17(9):2267-71.
[118]Reijo R, Lee TY, Salo P, et al. Diverse spermatogenic defects in humans caused by Y chromosome deletions encompassing a novel RNA-binding protein gene. Nature Genetics.1995;10(4):383-393.
[119]Kenan DJ, Query CC, Keene JD. RNA recognition:towards identifying determinants of specificity. Trends in Biochemical Sciences.1991;16(6):214-220.
[120]Burd CG, Dreyfuss G. Conserved structures and diversity of functions of RNA-binding proteins. Science.1994;265(5172):615-621.
[121]Elliott DJ, Millar MR, Oghene K, et al. Expression of RBM in the nuclei of human germ cells is dependent on a critical region of the Y chromosome long arm. Proceedings of the National Academy of Sciences of the United States of America.1997;94(8):3848-3853.
[122]Li HG, Ding XF, Zhao JX, Zuo MD, Xiong CL. Y chromosome microdeletions of 664 Chinese men with azoospermia or severe oligozoospermia. Zhonghua Yi Xue Yi Chuan Xue Za Zhi.2008 Jun;25(3):252-5.
[123]Song NH, Wu HF. Zhang W, Hua LX, Zhou ZM, Feng NH, Zhang J, Oiao D, Zhang JX. Detection of Y chromosome microdeletions in patients with severe oligozoospermia and azoospermia. Zhonghua Yi Xue Za Zhi.2006 May 30;86(20):1376-80.
[124]Ristanovic M, Bunjevacki V, Tulic C, Novakovic I, Ille T, Rdojkvic D, Nikolic A. Y Chromosome microdeletions in infertile male candidates for microfertiliza-tion.Srp Arh Celok Lek.2008 Mar-Apr; 136(3-4):126-30.
[125]Zhou H, Zhu JW, Li HG, Tang YP. Genetic defect in Chinese azoospermic patients and their relationship with reproductive hormone. Zhonghua Yi Xue Yi Chuan Xue Za Zhi.2009 Aug;26(4):427-30.
[126]S. Fernandes, S. Paracchini, L.H. Meyer, G. Floridia, C. Tyler-Smith, P.H. Vogt. A large AZFc deletion removes DAZ3/DAZ4 and nearby genes from men in Y haplogroup N. Am J Hum Genet,74 (2004), pp.180-187.
[127]K. Hucklenbroich, J. Gromoll, M. Heinrich, C. Hohoff, E. Nieschlag, M. Simoni. Partial deletions in the AZFc region of the Y chromosome occur in men with impaired as well as normal spermatogenesis. Hum Reprod,20 (2005), pp.191-197.
[128]M. de Llanos, J.L. Ballesca, C. Gazquez, E. Margarit, R. Oliva. High frequency of gr/gr chromosome Y deletions in consecutive oligospermic ICSI candidates. Hum Reprod,20 (2005), pp.216-220.
[129]S. Fernandes, K. Huellen, J. Goncalves, H. Dukal, J. Zeisler, E. Rajpert De Meyts et al. High frequency of DAZ1/DAZ2 gene deletions in patients with severe oligozoospermia. Mol Hum Reprod,8 (2002), pp.286-298.
[130]S. Repping, S.K.M. van Daalen, C.M. Korver et al.A family of human Y chromosome has dispersed throughout northern Eurasia despite a 1.8-Mb deletion in the azoospermia factor c region. Genomics,83 (2004), pp.1046-105.
[131]de Llanos M, Ballesca JL, Gazquez C, Margarit E, Oliva R. High frequency of gr/gr chromosome Y deletions in consecutive oligospermic ICSI candidates. Hum Reprod.2005;2:216-20.
[132][132] Li Y, Pan KJ, Wang L, Ren J. Association of gr/gr deletion in the AZFc region of Y chromosome with male infertility: a meta-analysis. Zhonghua Nan Ke Xue.2011 Jun;17(6):546-52.
[133]Kuijper EA, Blankenstein MA, Luttikhof LJ, Roek SJ, Overbeek A, Hompes PG, et al. Frequency distribution of polymorphisms in the FSH receptor gene in infertility patients of different ethnicity. Reprod Biomed Online. 2010;20:588-93.
[134]Dobson MJ, Pearlman RE, Karaiskakis A, Spyropoulos B, Moens PB. Synaptonemal complex proteins:occurrence, epitope mapping and chromosome disjunction. Journal of Cell Science.1994;107(10):2749-2760.
[135]Yuan L, Pelttari J, Brundell E, et al. The synaptonemal complex protein SCP3 can form multistranded, cross-striated fibers in vivo. Journal of Cell Biology. 1998;142(2):331-339.
[136]Yuan L, Liu JG, Zhao J, Brundell E, Daneholt B, Hoog C. The murine SCP3 gene is required for synaptonemal complex assembly, chromosome synapsis, and male fertility. Molecular Cell.2000;5(1):73-83.
[137]Miyamoto T, Hasuike S, Yogev L, et al. Azoospermia in patients heterozygous for a mutation in SYCP3. The Lancet.2003;362(9397):1714-1719.
[138]Yan W, Ma I, Burns KH, Matzuk MM. Haploinsufficiency of kelch-like protein homolog 10 causes infertility in male mice. Proceedings of the National Academy of Sciences of the United States of America. 2004;101(20):7793-7798.
[139]Wang S, Zheng H, Esaki Y, Kelly F, Yan W. Cullin3 is a KLHL10-interacting protein preferentially expressed during late spermiogenesis. Biology of Reproduction.2006;74(1):102-108.
[140]Dieterich K, Rifo RS, Faure AK, et al. Homozygous mutation of AURKC yields large-headed polyploid spermatozoa and causes male infertility. Nature Genetics.2007;39(5):661-665.
[141]Selhub J. Homocysteine metabolism. Annu Rev Nutr.1999; 19:217-46.
[142]Martin RH. Cytogenetic determinants of male fertility. Hum Reprod Update. 2008;14:379-90.
[143]Selice R, Di Mambro A, Garolla A, Ficarra V, Iafrate M, Ferlin A, et al. Spermatogenesis in Klinefelter syndrome. J Endocrinol Invest.2010;33:789-93.
[144]Lim AS, Fong Y, Yu SL. Estimates of sperm sex chromosome disomy and diploidy rates in a 47,XXY/46,XY mosaic Klinefelter patient. Hum Genet. 1999;104:405-9.
[145]Kruse R, Guttenbach M, Shartmann B, Schubert R, van der Ven H, Schmid M, et al. Genetic counselling in a patient with XXY/XXXY/XY mosaic Klinefelter's syndrome:estimate of sex chromosome aberrations in sperm before intracytoplasmic sperm injection. Fertil Steril.1998;69:432-85.
[146]Rives N, Joly G, Machy A, Simeon N, Leclerc P, Mace B. Assessment of sex chromosome aneuploidy in sperm nuclei from 47,XXY and 46,XY/47,XXY males:comparison with fertile and infertile males with normal karyotype. Mol Hum Reprod.2000;6:107-12.
[147]Estop AM, Cieply KM, Wakim A, Feingold E. Meiotic products of two reciprocal translocations studied by multicolor fluorescence in situ hybridization. Cytogenet Cell Genet.1998;83:193-8.
[148]Hall H, Hunt P, Hassold T.2006. Meiosis and sex chromosome aneuploidy: How meiotic errors cause aneuploidy; how aneuploidy causes meiotic errors. Curr Opin Genet Dev 16:323-329.
[149]Thomas NS, Hassold TJ.2003. Aberrant recombination and the origin of Klinefelter syndrome. Hum Reprod Update 9:309-317.
[150]Robinson DO, Jacobs PA.1999. The origin of the extra Y chromosome in males with a 47,XYY karyotype. Hum Mol Genet 8:2205-2209.
[151]Jacobs P, Dalton P, James R, Mosse K, Power M, Robinson D, Skuse D.1997. Turner syndrome:A cytogenetic and molecular study. Ann Hum Genet 61: 471-483.
[152]P.S Burgoyne. The role of sex chromosomes in mammalian germ cell differentiation Ann Biol Anim Biochim Biophys,18 (1978), pp.317-325.
[153]J Forejt.X-Y involvement in male sterility caused by autosome translocationsa hypothesis. P.G Crosignani, B.L Rubin, M Fraccaro (Eds.), Genetic control of gamete production and function. (Proc Serono Clinical Colloquia on Reproduction No.3), Academic Press, New York (1982), pp.261-273.
[154]Dada R, Gupta NP, Kucheria K. Semen cryopreservation in men with AZFc microdeletion. Clin Genet.2003;64:74-5.
[155]Hopps CV, Mielnik A, Goldstein M, Palermo GD, Rosenwakes Z, Schlegel PN. Detection of sperm in men with Y chromosome microdeletions of the AZFa, AZFb and AZFc regions. Hum Repord.2003 Aug; 18(8):1660-5.
[156]Shi YC, Cui YX, Wei L, Zhou YC, Shao Y, Xia XY, Shang XJ, Zhu WM, Huang YF. AZF microdeletions on the Y chromosome in infertile Chinese men:a five-year retrospective analysis. Zhonghua Nan Ke Xue.2010 Apr;16(4):314-9.
[157]Dai RL, Sun LK, Yang X, Li LL, Zhu HB, Liu RZ. Expansion and de novo occurrence of Y chromosome microdeletions occurring via natural vertical transmission in northeastern China. J Int Med Res.2012;40(3):1182-91.
[158]World Health Organization (WHO). WHO Laboratory Manual for the Examination of Human Semen and Semen-Cervical Mucus Interaction.4th ed. Cambridge, United Kingdom:Cambridge University Press; 1999.
[159]Shaffer LG, Slovak ML, Campbell LJ:ISCN 2009:an international system for human cytogenetic nomenclature (2009). Switzerland: Karger,2009,16-31.
[160]Simoni M, Bakker E, Krausz C. EAA/EMQN best practice guidelines for molecular diagnosis of y-chromosomal microdeletions. State of the art 2004. Int J Androl.2004,27(4):240-9.
[161]Zhou-Cun A, Yang Y, Zhang SZ, Zhang W, Lin L. Chromosomal abnormality and Y chromosome microdeletion in Chinese patients with azoospermia or severe oligozoospermia. Yi Chuan Xue Bao.2006 Feb;33(2):111-6.
[162]Maiburg M, Repping S, Giltay J. The genetic origin of Klinefelter syndrome and its effect on spermatogenesis. Fertil Steril 2012; 98(2):253-60.
[163]Ghorbel M, Gargouri Baklouti S, Ben Abdallah F Zribi N, Cherif M, Keskes R, Chakroun N, Sellami A, Belguith N, Kamoun H, et al. Chromosomal defects in infertile men with poor semen quality. J Assist Reprod Genet 2012;29(5):451-6.
[164]Ravel C,Chantot-Bastaraud S, Cretet J. Klinefelter syndrome:spermatogenesis and quality of gametes. Gynecol Obstet Fertil 2011;39(9):525-8.
[165]P.S Burgoyne. The role of sex chromosomes in mammalian germ cell differentiation Ann Biol Anim Biochim Biophys,18 (1978), pp.317-325
[166]Fullerton G, Hamilton M, Maheshwari A. Should non-mosaic Klinefelter syndrome men be labelled as infertile in 2009?. Hum Reprod 2010;25(3):588-97.
[167]Kliesch S, Zitzmann M, Behre HM. Fertility in patients with Klinefelter syndrome (47,XXY).Urologe A 2011;50(1):26-32.
[168]Houk CP, Rogol A, Lee PA. Fertility in men with Klinefleter syndrome. Pediatr Endocrinol Rev 2010; 8 Suppl 1:182-6.
[169]Ulug U, Bener F, Akman MA, Bahceci M. Partners of men with Klinefelter syndrome can benefit from assisted reproductive technologies. Fertil Steril. 2003 Oct;80(4):903-6.
[170]Sokol RZ. It's not all about the testes: medical issues in Klinefelter patients. Fertil Steril.2012 Aug;98(2):261-5.
[171]Mehta A, Paduch DA. Klinefelter syndrome: an argument for early aggressive hormonal and fertility management. Fertil Steril.2012 Aug;98(2):274-83.
[172]Uccellatore F, Padova G, Squatrito S. Reproductive hormone studies in three subjects with a Robertsonian translocation. J Endocrinol Invest.1983 Dec;6(6):479-84.
[173]J Forejt.X-Y involvement in male sterility caused by autosome translocationsa hypothesis P.G Crosignani, B.L Rubin, M Fraccaro (Eds.), Genetic control of gamete production and function. (Proc Serono Clinical Colloquia on Reproduction No.3), Academic Press, New York (1982), pp.261-273
[174]Dong Y, Du RC, Jiang YT, Wu J, Li LL, Liu RZ. Impact of chromosomal translocations on male infertility, semen quality, testicular volume and reproductive hormone levels. J Int Med Res.2012;40(6):2274-83.
[175]Matsuda T, Nonomura M, Yamamoto S, Hayashi K, Yoshida O. Sperm morphology in subfertile carriers of autosomal translocations. Int J Fertil1991;36(3):178-82.
[176]Yoshida A, Miura K, Shirai M. Cytogenetic survey of 1,007 infertile males.Urol Int1997;58(3):166-76.
[177]Brahem S, Elghezal H, Ghedir H, Landolsi H, Amara A, Ibala S, Gribaa M, Saad A,Mehdi M. Cytogenetic and molecular aspects of absolute teratozoospermia:comparison between polymorphic and monomorphic forms. Urology 2011;78(6):1313-9.
[178]Keymolen K, Staessen C, Verpoest W, Michiels A, Bonduelle M, Haentjens P, Vanderelst J, Liebaers I. A proposal for reproductive counselling in carriers of Robertsonian translocations:10 years of experience with preimplantation genetic diagnosis. Hum Reprod.2009 Sep;24(9):2365-71.
[179]Anton E, Vidal F, Blanco J. Interchromosomal effect analyses by sperm FISH: incidence and distribution among reorganization carriers. Syst Biol Reprod Med.2011 Dec;57(6):268-78.
[180]Chang EM, Han JE, Kwak IP, Lee WS, Yoon TK, Shim SH. Preimplantation genetic diagnosis for couples with a Robertsonian translocation:practical information for genetic counseling. J Assist Reprod Genet.2012 Jan;29(1):67-75.
[181]Zhao H, Xu J, Zhang H, Sun J, Sun Y, Wang Z, Liu J, Ding Q, Lu S, Shi R, You L, Qin Y, Zhao X, Lin X, Li X, Feng J, Wang L, Trent JM, Xu C, Gao Y, Zhang B, Gao X, Hu J, Chen H, Li G, Zhao J, Zou S, Jiang H, Hao C, Zhao Y, Ma J, Zheng SL, Chen ZJ.A genome-wide association study reveals that variants within the HLA region are associated with risk for nonobstructive azoospermia. Am J Hum Genet.2012 May 4;90(5):900-6.
[182]Teng YN, Chang YP, Tseng JT, Kuo PH, Lee IW, Lee MS, Kuo PL. A single-nucleotide polymorphism of the DAZL gene promoter confers susceptibility to spermatogenic failure in the Taiwanese Han. Hum Reprod 2012;27(9):2857-65.
[183]Jensen TK, Andersson AM, Hjollund NH, Scheike T, Kolstad H, Giwercman A, Henriksen TB, Ernst E, Bonde JP, Olsen J, McNeilly A, Groome NP, Skakkebaek NE.Inhibin B as a serum marker of spermatogenesis:correlation to differences in sperm concentration and follicle-stimulating hormone levels. A study of 349 Danish men. J Clin Endocrinol Metab.1997 Dec;82(12):4059-63.
[184]Bergmann M, Behre HM, Nieschlag E.Serum FSH and testicular morphology in male infertility. Clin Endocrinol (Oxf).1994 Jan;40(1):133-6.
[185]Arai T, Kitahara S, Horiuchi S, Sumi S, Yoshida K. Relationship of testicular volume to semen profiles and serum hormone concentrations in infertile Japanese males. Int J Fertil Womens Med1998;43(1):40-7.
[186]Bayasgalan G, Naranbat D, Radnaabazar J, Lhagvasuren T, Rowe PJ. Male infertility, risk factors in Mongolian men. Asian J Androl 2004;6(4):305-11.
[187]Bak CW, Byun JS, Lee JH, Park JH, Lee KA, Shim SH. Clinical and social characteristics of Korean men with Klinefelter syndrome Int J Urol. 2012;19(5):443-9.
[188]Aribarg A, Kenkeerati W, Vorapaiboonsak V, Leepipatpaiboon S, Farley TM. Testicular volume, semen profile and serum hormone levels in fertile Thai males. Int J Androl 1986;9(3):170-80.
[189]de Gouveia Brazao CA, Pierik FH, Erenpreiss Y, de Jong FH, Dohle GR, Weber RF. The effect of cryptorchidism on inhibin B in a subfertile population. Clin Endocrinol (Oxf) 2003;59(1):136-41.
[190]Hammar M, Berg AA. Impaired Leydig cell function in vitro in testicular tissue from human males with "Sertoli cell only" syndrome. Andrologia.1985 Jan-Feb;17(1):37-41.
[191]Andersson AM, J(?)rgensen N, Frydelund-Larsen L, Rajpert-De Meyts E, Skakkebaek NE. Impaired Leydig cell function in infertile men:a study of 357 idiopathic infertile men and 318 proven fertile controls. J Clin Endocrinol Metab.2004 Jul;89(7):3161-7.
[192]Holm M, Rajpert-De Meyts E, Andersson AM, Skakkebaek NE. Leydig cell micronodules are a common finding in testicular biopsies from men with impaired spermatogenesis and are associated with decreased testosterone/LH ratio. J Pathol.2003 Mar;199(3):378-86.
[193]Kyriacou C, Kottaridis PD, Eliahoo J, McKeag N, Bomford J, McGarrigle HH, Linch DC, Mackinnon S, Chatterjee R. Germ cell damage and Leydig cell insufficiency in recipients of nonmyeloablative transplantation for haematological malignancies. Bone Marrow Transplant.2003 Jan;31(1):45-50.
[194]Wu O, Wang H, Liu YL, Xu Y, Wang P, Shi HJ, Feng Y. Sequence tagged sites of AZFc microdeletion in Chinese Han population. Zhonghua Nan Ke Xue.2011 May;17(5):391-5.
[195]Nie ZY, Wu HF, Zhang N, Guo LN, Zhao SY, Zhen XL, Lu CT. Influence of male age on the outcome of conventional IVF-ET. Zhonghua Nan Ke Xue 2012;18(3):248-52.
[196]Cui YQ, Gao ES, Zhou WJ, Wu JQ, Yuan W. Association between age and quality of semen in Chinese males with normal fertility. Zhonghua Liu Xing Bing Xue Za Zhi 2009; 30(9):899-902.
[197]Sartorius GA, Nieschlag E. Paternal age and reproduction. Hum Reprod Update 2010;16(1):65-7.
[198]Liu Y, Kong XD, Wu QH, Li G, Song L, Sun YP. Karyotype analysis in large-sample infertile couples living in Central China:a study of 14965 couples. J Assist Reprod Genet.2013 Apr;30(4):547-53.
[199]Samli H, Samli MM, Solak M, Imirzalioglu N.Genetic anomalies detected in patients with non-obstructive azoospermia and oligozoospermia. Arch Androl.2006 Jul-Aug;52(4):263-7
[200]Ng PP, Tang MH, Lau ET, Ng LK, Ng EH, Tam PC, Yeung WS, Ho PC.Chromosomal anomalies and Y-microdeletions among Chinese subfertile men in Hong Kong. Hong Kong Med J.2009 Feb;15(1):31-8.
[201]Ghorbel M, Gargouri Baklouti S, Ben Abdallah F, Zribi N, Cherif M, Keskes R, Chakroun N, Sellami A, Belguith N, Kamoun H, Fakhfakh F, Ammar-Keskes L. Chromosomal defects in infertile men with poor semen quality. J Assist Reprod Genet.2012 May;29(5):451-6.
[202]Fu L, Xiong DK, Ding XP, Li C, Zhang LY, Ding M, Nie SS, Quan Q. Genetic screening for chromosomal abnormalities and Y chromosome microdeletions in Chinese infertile men. J Assist Reprod Genet.2012 Jun;29(6):521-7.
[203]Dul EC, van Echten-Arends J, Groen H, Dijkhuizen T, Land JA, van Ravenswaaij-Arts CM. Chromosomal abnormalities in azoospermic and non-azoospermic infertile men:numbers needed to be screened to prevent adverse pregnancy outcomes. Hum Reprod.2012 Sep;27(9):2850-6.
[204]Alhalabi M, Kenj M, Monem F, Mahayri Z, Abou Alchamat G, Madania A.High prevalence of genetic abnormalities in Middle Eastern patients with idiopathic non-obstructive azoospermia. J Assist Reprod Genet.2013 Jun;30(6):799-805.
[205]Pylyp LY, Spinenko LO, Verhoglyad NV, Zukin VD.Chromosomal abnormalities in patients with oligozoospermia and non-obstructive azoospermia. J Assist Reprod Genet.2013 Jun;30(5):729-32.
[2]De Kretser DM and Baker HWG. Infertility in men: recent advances and continuing controversies. J Clin Endocrinol Metab.1999; 84:3443-3450.
[3]Ferlin A, Arredi B, Foresta C. Genetic causes of male infertility. Reprod Toxicol.2006 Aug;22(2):133-41.
[4]O'Flynn O'Brien KL, Varghese AC, Agarwal A. The genetic causes of male factor infertility:a review. Fertil Steril.2010 Jan;93(1):1-12.
[5]Cooper TG, Noonan E, Von Eckardstein S, Auger J, Baker HWG, Behre HM, Haugen TB, Kruger T, Wang C. World Health Organization reference values for human semen characteristics. Human Reproduction Update.2009; 16 (3): 231-5.
[6]Hargreave TB, McGowan B, Harvey J, McParland M, Elton RA. Is a male infertility clinic of any use?. Br. J. Urol.1986 April; 58 (2):188-93.
[7]Hwang K, Walters RC, Lipshultz LI. Contemporary concepts in the evaluation and management of male infertility. Nat. Rev. Urol.2011 February; 8 (2):86-94.
[8]Roze C, Touraine P, Leger J, de Roux N. Congenital hypogonadotropic hypogonadism. Ann Endocrinol (Paris).2009 Mar;70(1):2-13.
[9]Nilsson LA, Roepstorff C, Kiens B, Billig H, Ling C. Prolactin suppresses malonyl-CoA concentration in human adipose tissue. Horm Metab Res.2009 Oct;41(10):747-51.
[10]Reisch N, Flade L, Scherr M, Rottenkolber M, Pedrosa Gil F, Bidlingmaier M, Wolff H, Schwarz HP, Quinkler M, Beuschlein F, Reincke M. High prevalence of reduced fecundity in men with congenital adrenal hyperplasia. J Clin Endocrinol Metab.2009 May;94(5):1665-70.
[11]Devoto C E, Madariaga A M, Fernandez W. Congenital adrenal hyperplasia causing male infertility. Report of one case.Rev Med Chil.2011 Aug; 139(8):1060-5.
[12]Budzynska E, Ben-Skowronek I. Testicular adrenal rest tumours in boys with congenital adrenal hyperplasia:case report and literature review. Pediatr Endocrinol Diabetes Metab.2011;17(4):239-42.
[13]Nikoobakht MR, Aloosh M, Nikoobakht N, Mehrsay AR, Biniaz F, Karjalian MA. The role of hypothyroidism in male infertility and erectile dysfunction. Urol J.2012 Winter;9(1):405-9.
[14]Purvis K, Christiansen E. Infection of the male reproductive tract. Impact, diagnosis and treatment in relation to male infertility. Int J Androl.1993:16:1-13.
[15]Goluboff ET, Stifelman MD, Fisch H. Ejaculatory duct obstruction in infertile men. Urology.1995:45:925-931.
[16]Di Carlo A. Sexually transmitted diseases syndromic approach:urethral discharge. G Ital Dermatol Venereol.2012 Aug;147(4):389-94.
[17]Belmonte IG, Martin de Serrano MN. Partial obstruction of the seminal path, a frequent cause of oligozoospermia in men. Hum Reprod.1998:13:3402-3405.
[18]Li H, Wen Q, Li H, Zhao L, Zhang X, Wang J, Cheng L, Yang J, Chen S, Ma X, Wang B. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) in Chinese patients with congenital bilateral absence of vas deferens. J Cyst Fibros.2012 Jul;11(4):316-23.
[19]Pollack AE, et al. (2007). Female and male sterilization. In RA Hatcher et al., eds., Contraceptive Technology,19th ed., pp.361-401. New York:Ardent Media.
[20]Labrecque M, Nazerali H, Mondor M, Fortin V, Nasution M. Effectiveness and complications associated with 2 vasectomy occlusion techniques. J Urol. 2002 Dec; 168(6):2495-8
[21]Fode M, Krogh-Jespersen S, Brackett NL, Ohl DA, Lynne CM, S(?)nksen J. Male sexual dysfunction and infertility associated with neurological disorders. Asian J Androl.2012 Jan;14(1):61-8.
[22]Isidro ML. Sexual dysfunction in men with type 2 diabetes. Postgrad Med J. 2012 Mar;88(1037):152-9.
[23]Aust TR, Lewis-Jones DI. Retrograde ejaculation and male infertility. Hosp Med.2004 Jun;65(6):361-4.
[24]Amano T, Imao T, Takemae K, Yamauchi K. Ejaculatory disorder caused by doxazosin administration for blood pressure control in patient with pheo-chomocytoma. Hinyokika Kiyo.2009 Jun;55(6):377-80.
[25]Rowland D, McMahon CG, Abdo C, Chen J, Jannini E, Waldinger MD, Ahn TY. Disorders of orgasm and ejaculation in men. J Sex Med.2010 Apr;7(4 Pt 2):1668-86.
[26]Kolon FT, Patel PR, Huff SD. Cryptorchidism:diagnosis, treatment and long-term prognosis. Urol Clin North Am.2004;31:469-80.
[27]Hadziselimovic F, Herzog B. The importance of both and early orchidopexy and germ cell maturation for fertility. Lancet.2001;358:1156-7.
[28]Pereira JR, Neves S, Leite F, Baptista C, Santos E, Ferrao A, Figueiredo C. Cryptorchidism in adolescence. Acta Med Port.2011 Dec;24 Suppl 3:715-8.
[29]La Vignera S, Calogero AE, Condorelli R, Marziani A, Cannizzaro MA, Lanzafame F, Vicari E. Cryptorchidism and its long-term complications. Eur Rev Med Pharmacol Sci.2009 Sep-Oct;13(5):351-6.
[30]Agoulnik AI, Huang Z, Ferguson L. Spermatogenesis in cryptorchidism. Methods Mol Biol.2012;825:127-47.
[31]Pellati D, Mylonakis I, Bertoloni G, Fiore C, Andrisani A, Ambrosini G, Armanini D. Genital tract infections and infertility. Eur J Obstet Gynecol Reprod Biol.2008 Sep;140(1):3-1l.
[32]Hofny ER, Ali ME, Taha EA, Nafeh HM, Sayed DS, Abdel-Azeem HG, Abdou EF, Kamal GM, Mostafa T. Semen and hormonal parameters in men with chronic hepatitis C infection. Fertil Steril.2011 Jun 30;95(8):2557-9.
[33]Chen JW, Cui Y, Zhang XX. Investigate the impact of hepatitis B virus infection on sperm DNA integrity. Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi.2011 Oct;25(5):345-7.
[34]Baker BW, Surratt JK, Run W. Missed testicular torsion presenting with male infertility and erectile dysfunction. Zhonghua Nan Ke Xue.2005 Aug;11(8):615-6.
[35]Mongiat-Artus P. Torsion of the spermatic cord and testicular annexes. Ann Urol (Paris).2004 Feb;38(1):25-34.
[36]Filho DW, Torres MA, Bordin AL, Crezcynski-Pasa TB, Boveris A. Spermatic cord torsion, reactive oxygen and nitrogen species and ischemia-reperfusion injury. Mol Aspects Med.2004 Feb-Apr;25(1-2):199-210.
[37]Dokmeci D. Testicular torsion, oxidative stress and the role of antioxidant therapy. Folia Med (Plovdiv).2006;48(3-4):16-21.
[38]Zilberman D, Inbar Y, Heyman Z, Shinhar D, Bilik R, Avigad I, Jonas P, Ramon J, Mor Y.Torsion of the cryptorchid testis--can it be salvaged? J Urol.2006 Jun;175(6):2287-9.
[39]Aning J, Gillatt D. When should patients with varicocoele be referred? Practitioner.2012 Apr;256(1750):17-20,2-3.
[40]Kroese AC, de Lange NM, Collins J, Evers JL. Surgery or embolization for varicoceles in subfertile men. Cochrane Database Syst Rev.2012 Oct 17;10:CD000479.
[41]Guo SJ, Sun ZJ, Li W. New insights about the early diagnosis of fertility impairment in varicoceles:the DNA repair gene example. Med Hypotheses. 2012Apr;78(4):536-8.
[42]Keene DJ, Sajad Y, Rakoczy G, Cervellione RM.Testicular volume and semen parameters in patients aged 12 to 17 years with idiopathic varicocele. J Pediatr Surg.2012 Feb;47(2):383-5.
[43]Calogero A, Polosa R, Perdichizzi A, Guarino F, La Vignera S, Scarfia A, Fratantonio E, Condorelli R, Bonanno O, Barone N, Burrello N, D'Agata R, Vicari E. Cigarette smoke extract immobilizes human spermatozoa and induces sperm apoptosis. Reprod Biomed Online.2009 Oct; 19(4):564-71.
[44]Sepaniak S, Forges T, Monnier-Barbarino P. Cigarette smoking and fertility in women and men.Gynecol Obstet Fertil.2006 Oct;34(10):945-9.
[45]Sermondade N, Elloumi H, Berthaut I, Mathieu E, Delarouziere V, Ravel C, Mandelbaum J. Progressive alcohol-induced sperm alterations leading to spermatogenic arrest, which was reversed after alcohol withdrawal. Reprod Biomed Online.2010 Mar;20(3):324-7.
[46]Mathur PP, D' Cruz SC. The effect of environmental contaminants on testicular function. Asian J Androl.2011 Jul;13(4):585-91.
[47]Wong EW, Cheng CY. Impacts of environmental toxicants on male reproductive dysfunction. Trends Pharmacol Sci.2011 May;32(5):290-9.
[48]Pacey AA. Environmental and lifestyle factors associated with sperm DNA damage. Hum Fertil (Camb).2010 Dec; 13(4):189-93.
[49]Bonde, J.P. (1996) Environmental Factors. In Comhaire, F.H. (ed.), Male Infertility, Clinical Investigation, Cause Evaluation and Treatment. Chapman and Hall, London, pp.267-284.
[50]Spira, A. and Multigner, L. (1998). The effect of industrial and agricultural pollution on human spermatogenesis. Hum. Reprod.,13,2041-2042.
[51]Singh DK, Hersey K, Perlis N, Crook J, Jarvi K, Fleshner N. The effect of radiation on semen quality and fertility in men treated with brachytherapy for early stage prostate cancer. J Urol.2012 Mar;187(3):987-9.
[52]P Thonneau, L Bujan, L Multigner and R Mieusset. Occupational heat exposure and male fertility:a review. Human Reproduction Volume 13, Issue 8Pp.2122-2125.
[53]Dada R, Kumar R, Shamsi MB, Kumar R, Kucheria K, Sharma RK, et al. Higher frequency of Yq microdeletions in sperm DNA as compared to DNA isolated from blood. Asian J Androl.2007;9:720-2.
[54]Yoshida A, Miura K, Shirai M. Cytogenetic survey of 1,007 males. Urol Int. 1997;58:166-76
[55]Hassold T, Hunt P. To err (meiotically) is human: the genesis of human aneuploidy. Nat Rev Genet 2001; 2:280-91.
[56]C. Foresta, A. Ferlin, L. Gianaroli, B. DallapiccolaGuidelines for the appropriate use of genetic tests in infertile couples. Eur J Hum Genet,10 (2002), pp.303-312.
[57]C. Foresta, A. Garolla, L. Bartoloni, A. Bettella, A. Ferlin. Genetic abnormalities among severely oligospermic men who are candidates for intracytoplasmic sperm injection. J Clin Endocrinol Metab,90 (2005), pp. 152-156.
[58]C. Foresta, C. Galeazzi, A. Bettella, M. Stella, C. Scandellari. High incidence of sperm sex chromosomes aneuploidies in two patients with Klinefelter's syndrome.
[59]C.Foresta, A. Ferlin, L. Gianaroli, B. Dallapiccola. Guidelines for the appropriate use of genetic tests in infertile couples. Eur J Hum Genet,10 (2002), pp.303-312.
[60]Pina-Neto JM, Carrara RC, Bisinella R, Mazzucatto LF, Martins MD, Sartoratto E, Yamasaki R. Somatic cytogenetic and azoospermia factor gene microdeletion studies in infertile men. Braz J Med Biol Res.2006 Apr;39(4):555-61.
[61]Groth KA, Skakkebaek A, Host C, Gravholt CH, Bojesen A. Klinefelter Syndrome--A Clinical Update.J Clin Endocrinol Metab.2012 Nov 1.
[62]Balkan M, Tekes S, Gedik A. Cytogenetic and Y chromosome microdeletion screening studies in infertile males with Oligozoospermia and Azoospermia in Southeast Turkey. J Assist Reprod Genet 2008 Nov-Dec;25(11-12):559-65.
[63]Garcia-Quevedo L, Blanco J, Sarrate Z, Catala V, Bassas L, Vidal F. Hidden mosaicism in patients with Klinefelter's syndrome:implications for genetic reproductive counselling. Hum Reprod 2011;26(12):3486-93.
[64]Tincani BJ, Mascagni BR, Pinto RD, Guaragna-Filho G, Castro CC, Sewaybricker LE, Viguetti-Campos NL, Marques-de-Faria AP, Maciel-Guerra AT, Guerra-Junior G. Klinefelter syndrome: an unusual diagnosis in pediatric patients. J Pediatr (Rio J).2012 Jul;88(4):323-7.
[65]Messina MF,Sgro DL, Aversa T,Pecoraro M, Valenzise M,De Luca F.A characteristic cognitive and behavioral pattern as a clue to suspect Klinefelter syndrome in prepubertal age. J Am Board Fam Med.2012 Sep-Oct;25(5):745-9.
[66]Zhao LM, Jiang H, Hong K, Huang J, Tang WH, Mao JM, Qiao J, Liu P, Lian Y, Ma LL. Successful microdissection testicular sperm extraction in patients with nonmosaic Klinefelter syndrome:three cases report. Beijing Da Xue Xue Bao 2012;44(4):547-50.
[67]Selice R,Di Mambro A,Garolla A,Ficarra V,Iafrate M,Ferlin A,Foresta C.Spermatogenesis in Klinefelter syndrome. J Endocrinol Invest 2010; 33(1l):789-93.
[68]Van Saen D, Gies I, De Schepper J, Tournaye H, Goossens E. Can pubertal boys with Klinefelter syndrome benefit from spermatogonial stem cell banking?. Hum Reprod 2012; 27(2):323-30.
[69]Oates R:The natural history of endocrine function and spermatogenesis in Klinefelter syndrome:what the data show. Fertil Steril 2012 Aug;98(2):266-73.
[70]A. Ferlin, A. Garolla, C. Foresta. Chromosome abnormalities in sperm of individuals with constitutional sex chromosomal abnormalities. Cytogenet Genome Res,111 (2005), pp.310-316.
[71]B.E. Reubinoff, D. Abeliovich, M. Werner, J.G. Schenker, A. Safran, A. Lewin. A birth in non-mosaic Klinefelter's syndrome after testicular fine needle aspiration, intracytoplasmic sperm injection and preimplantation genetic diagnosis. Hum Reprod,13 (1998), pp.1887-1892.
[72]R. Ron-El, D. Strassburger, S. Gelman-Kohan, S. Friedler, A. Raziel, Z. Appelman. A 47,XXY fetus conceived after ICSI of spermatozoa from a patient with non-mosaic Klinefelter's syndrome:case report. Hum Reprod,15 (2000), pp.1804-1806.
[73][73] Yatsenko AN, Yatsenko SA, Weedin JW, Lawrence AE, Patel A, Peacock S, Matzuk MM, Lamb DJ, Cheung SW, Lipshultz LI. Comprehensive 5-year study of cytogenetic aberrations in 668 infertile men. J Urol.2010 Apr; 183(4):1636-42.
[74]Rappold GA. The pseudoautosomal regions of the human sex chromosomes. Hum Genet.1993 Oct;92(4):315-24.
[75]Ferguson-Smith MA. X-Y chromosomal interchange in the aetiology of true hermaphroditism and of XX Klinefelter's syndrome. Lancet.1966 Aug 27;2(7461):475-6.
[76]Weil D, Wang I, Dietrich A, Poustka A, Weissenbach J, Petit C.Highly homologous loci on the X and Y chromosomes are hot-spots for ectopic recombinations leading to XX maleness. Nat Genet.19.
[77]Dada R, Ahmed ME, Talwar R, Kucheria K. Clinical and Genetic study in a XX (SRY negative) male. Int J Med.2002.
[78]Martin RH. Cytogenetic determinants of male fertility. Hum Reprod. Update 2008 Jul-Aug;14(4):379-90.
[79]Ross JL, Roeltgen DP, Kushner H, Zinn AR, Reiss A, Bardsley MZ, McCauley E, Tartaglia N. Behavioral and social phenotypes in boys with 47,XYY syndrome or 47,XXY Klinefelter syndrome. Pediatrics.2012 Apr;129(4):769-78.
[80]C. Alves, F. Carvalho, N. Cremades, M. Sousa, A. Barros:Unique [Y;13] translocation in a male with oligozoospermia:cytogenetic and molecular studies. Eur J Hum Genet,10 (2002), pp.467-474.
[81]P.H. Vogt, A. Edelmann, P. Hirschmann, M.R. Kohler. The azoospermia factor [AZF] of the human Y chromosome in Yq11:function and analysis in spermatogenesis. Reprod Fertil Dev,7 (1995), pp.685-693.
[82]Yumura Y, Murase M, Katayama K, Segino M, Aizawa Y, Kuroda SN, Noguchi K. Y-autosome translocation associated with male infertility: a case report; Hinyokika Kiyo.2012 Jun;58(6):307-10.
[83]Kumar R, Shamsi MB, Gaznavi MI, Jena M, Kucheria K, Kumar R, et al. Structural chromosomal anomalies and their association with reproductive failure. Obstet Gynecol Today.2007; 12:152-4.
[84]Hamerton JL, Canning N, Ray M, Smith S. A cytogenetic survey of 14,069 newborn infants:incidence of chromosomal abnormalities. Clin Genet. 1975;8:223-43.
[85]E. Therman, M. Susman. Human chromosome:structure, behaviour and effects:Springer-Verlag, New York (1993) pp.273-287.
[86]86] Huang J, Lian Y, Qiao J, Liu P. Clinical characteristics and preimplantation genetic diagnosis for male Robertsonian translocations. Beijing Da Xue Xue Bao 2012 Aug 18;44(4):544-6.
[87]Meza-Espinoza JP, Anguiano LO, Rivera H. Chromosomal abnormalities in couples with reproductive disorders. Gynecol Obstet Invest.2008;66:237-40.
[88]M. De Braekeleer, T.N. Dao. Cytogenetic studies in male infertility:a review; Hum Reprod,6 (1991), pp.245-250.
[89]Gary L Harton and Helen G Tempest. Chromosomal disorders and male infertility Asian Journal of Andrology (2012) 14,32-39.
[90]Feuk L, MacDonald J. R, Tang T, Carson A. R, Li M, et al. (2005) Discovery of human inversion polymorphisms by comparative analysis of human and chimpanzee DNA sequence assemblies. PLoS Genet 1:e56.
[91]Daniel A, Hook EB, Wulf G. Risks of unbalanced progeny at amniocentesis to carriers of chromosome rearrangements:data from United States and Canadian laboratories. Am J Med Genet.1989;31:14-53.
[92]Shah K, Sivapalan G, Gibbons N, Tempest H, Griffin DK. The genetic basis of infertility. Reproduction 2003; 126:13-25
[93]Coyne J. A, Aulard S, Berry A (1991) Lack of underdominance in a naturally-occurring pericentric inversion in Drosophila melanogaster and its implications for chromosome evolution. Genetics 129:791-802.
[94]Cortes-Gutierrez EI, Cerda-Flores RM, Davila-Rodriguez MI, Hernandez-Herrera R, Vargas-Villarreal J, Leal-Garza CH. Chromosomal abnormalities and polymorphisms in Mexican infertile men. Arch Androl 2004 Jul-Aug;50(4):261-5.
[95]Sato H, Miyamoto T, Yogev L, et al. Polymorphic alleles of the human MEI1 gene are associated with human azoospermia by meiotic arrest. Journal of Human Genetics.2006;51(6):533-540.
[96]Miyamoto T, Tsujimura A, Miyagawa Y, et al. Single nucleotide 4 polymorphism in the UBR2 gene may be a genetic risk factor for Japanese patients with azoospermia by meiotic arrest. Journal of Assisted Reproduction and Genetics.2011;28(8):743-746.
[97]Miyakawa H, Miyamoto T, Koh E, et al. Single-nucleotide polymorphisms in the SEPTIN12 gene may be a genetic risk factor for Japanese patients with sertoli cell-only syndrome. Journal of Andrology. In press.
[98]Qin Y, Xia Y, Wu W, Han X, Lu C, Ji G, Chen D, Wang H, Song L, Wang S, Wang X. Genetic variants in microRNA biogenesis pathway genes are associated with semen quality in a Han-Chinese population. Reprod Biomed Online.2012 Apr;24(4):454-61.
[99]Blennow E, Bui T, Kristofferson U, Vujic M, Annerens G, Holmberg F, Nordenskjold M. Swedish survey on extra structurally abnormal chromosomes in 39105 consecutive prenatal diagnoses:prevalence and characterization by fluorescence in situ hybridization. Prenat Diagn 1994.141019-1028.1028.
[100]Warburton U. De novo balanced chromosome rearrangements and extra marker chromosomes identified at prenatal diagnosis:clinical significance and distribution of breakpoints. Am J Hum Genet 1991.49(5)995-1013.1013.
[101]Crolla J. FISH and molecular studies of autosomal supernumerary marker chromosomes excluding those derived from chromosome 15:II. Review of the literature. Am Med Genet 1998.75367-381.381.
[102]Carrasco J J L, Otewro G A, Vilar M M C, Garcia M J L, Troyano L J M, Lopez R C C, Parache H J. Small marker chromosomes in a series of 1000 prenatal diagnoses by amniocentesis. Ann Gene 1990.3340-42.42.
[103]Sachs E S, Van Hemel J O, Den Hollander J C, Jahoda M G. Marker chromosomes in a series of 10,000 prenatal diagnoses:cytogenetic and follow-up studies. Prena Diagn 1987.781-89.89.
[104]Steinbach P, Djalali M, Hansmann I, Kattner F, Meisel-Stosiek M, Probeck H D, Schmidt A, Wolf M. The genetic significance of bisatellited marker chromosomes. Hum Genet 1983.65155-164.164.
[105]Tiepolo L, Zuffardi O. Localization of factors controlling spermatogenesis in the nonfluorescent portion of the human Y chromosome long arm. Hum Genet 1976:34:119-124.
[106]Kim MJ, Choi HW, Park SY, Song IO, Seo JT, Lee HS. Molecular and cytogenetic studies of 101 infertile men with microdeletions of Y chromosome in 1,306 infertile Korean men. J Assist Reprod Genet.2012 June:29(6):539-46.
[107]Ristanovic M, Bunjevacki V, Tulic C, Novakovic I, Perovic V, Lukovic LJ, Milasin J. Prevalence of Y chromosome microdeletions in infertile men with severe oligozoospermia in Serbia. Genet Couns.2007;18(3):337-42.
[108]Mirfakhraie R, Mirzajani F, Kalantar SM, Montazeri M, Salsabili N, Pourmand GR, Houshmand M. High prevalence of AZFb microdeletion in Iranian patients with idiopathic non-obstructive azoospermia. Indian J Med Res.2010 Sep;132:265-70.
[109]Fu J, Li L, Lu G. Relationship between microdeletion on Y chromosome and patients with idiopathic azoospermia and severe oligozoospermia in the Chinese.China Med J (Engl).2002 Jan; 115(1):72-5.
[110]Li HG, Ding XF, Zhao JX, Zuo MD, Xiong CL. Y chromosome microdeletions of 664 Chinese men with azoospermia or severe oligozoospermia. Zhonghua Yi Xue Yi Chuan Xue Za Zhi.2008 Jun;25(3):252-5.
[111]Liu YF, Ou JP, Zhou CQ, Wang Q, Wang ZL. Screening for the microdeletions of azoospermia factor on the Y chromosome in male infertile patients from Guangzhou. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2007 Oct;24(5):564-6.
[112]Zhu YJ, Liu SY, Wang H, Wei P, Ding XP. The prevalence of azoospermia factor microdeletion on the Y chromosome of Chinese infertile men detected by multi-analyte suspension array technology. Asian Androl.2008 Nov;10(6):873-81.
[113]Vogt PH, Edelmann A, Kirsch S, Henegariu O, Hirschmann P, Kiesewetter F, Kohn FM, Schill WB, Farah S, Ramos C, Hartmann M, Hartschuh W, Meschede D, Behre HM, Castel A, Nieschlag E, Weidner W, Grone HJ, Jung A, Engel W, Haidl G. Human Y chromosome azoospermia factors (AZF) mapped to different subregions in Yqll.Hum Mol Genet.1996 Ju1;5(7):933-43.
[114]Kent-First M,Muallem A, et al:Defining regions of the Y-chromosome responsible for male infertility and identification of a fourth AZF region (AZFd) by Y-chromosome microdeletion detection. Mol Reprod 1999:53:27-41.
[115]Sargent CA, Boucher CA, Kirsch S, Brown G, Weiss B, Trundley A, Burgoyne P, Saut N. Durand C, Levy N, Terriou P, Hargreave T, Cooke H, Mitchell M, Rappold GA, Affara NA. The critical region of overlap defining the AZFa male infertility interval of proximal Yq contains three transcribed sequences. J Med Genet1999;36:670-7.
[116]Lahn BT, Page DC. Functional coherence of the human Y chromosome. Sciencel997;278:675-80.
[117]Rolf C, Gromoll J, Simoni M, Nieschlag E. Natural transmission of a partial AZFb deletion of the Y chromosome over three generations:case report. Hum Reprod.2002 Sep;17(9):2267-71.
[118]Reijo R, Lee TY, Salo P, et al. Diverse spermatogenic defects in humans caused by Y chromosome deletions encompassing a novel RNA-binding protein gene. Nature Genetics.1995;10(4):383-393.
[119]Kenan DJ, Query CC, Keene JD. RNA recognition:towards identifying determinants of specificity. Trends in Biochemical Sciences.1991;16(6):214-220.
[120]Burd CG, Dreyfuss G. Conserved structures and diversity of functions of RNA-binding proteins. Science.1994;265(5172):615-621.
[121]Elliott DJ, Millar MR, Oghene K, et al. Expression of RBM in the nuclei of human germ cells is dependent on a critical region of the Y chromosome long arm. Proceedings of the National Academy of Sciences of the United States of America.1997;94(8):3848-3853.
[122]Li HG, Ding XF, Zhao JX, Zuo MD, Xiong CL. Y chromosome microdeletions of 664 Chinese men with azoospermia or severe oligozoospermia. Zhonghua Yi Xue Yi Chuan Xue Za Zhi.2008 Jun;25(3):252-5.
[123]Song NH, Wu HF. Zhang W, Hua LX, Zhou ZM, Feng NH, Zhang J, Oiao D, Zhang JX. Detection of Y chromosome microdeletions in patients with severe oligozoospermia and azoospermia. Zhonghua Yi Xue Za Zhi.2006 May 30;86(20):1376-80.
[124]Ristanovic M, Bunjevacki V, Tulic C, Novakovic I, Ille T, Rdojkvic D, Nikolic A. Y Chromosome microdeletions in infertile male candidates for microfertiliza-tion.Srp Arh Celok Lek.2008 Mar-Apr; 136(3-4):126-30.
[125]Zhou H, Zhu JW, Li HG, Tang YP. Genetic defect in Chinese azoospermic patients and their relationship with reproductive hormone. Zhonghua Yi Xue Yi Chuan Xue Za Zhi.2009 Aug;26(4):427-30.
[126]S. Fernandes, S. Paracchini, L.H. Meyer, G. Floridia, C. Tyler-Smith, P.H. Vogt. A large AZFc deletion removes DAZ3/DAZ4 and nearby genes from men in Y haplogroup N. Am J Hum Genet,74 (2004), pp.180-187.
[127]K. Hucklenbroich, J. Gromoll, M. Heinrich, C. Hohoff, E. Nieschlag, M. Simoni. Partial deletions in the AZFc region of the Y chromosome occur in men with impaired as well as normal spermatogenesis. Hum Reprod,20 (2005), pp.191-197.
[128]M. de Llanos, J.L. Ballesca, C. Gazquez, E. Margarit, R. Oliva. High frequency of gr/gr chromosome Y deletions in consecutive oligospermic ICSI candidates. Hum Reprod,20 (2005), pp.216-220.
[129]S. Fernandes, K. Huellen, J. Goncalves, H. Dukal, J. Zeisler, E. Rajpert De Meyts et al. High frequency of DAZ1/DAZ2 gene deletions in patients with severe oligozoospermia. Mol Hum Reprod,8 (2002), pp.286-298.
[130]S. Repping, S.K.M. van Daalen, C.M. Korver et al.A family of human Y chromosome has dispersed throughout northern Eurasia despite a 1.8-Mb deletion in the azoospermia factor c region. Genomics,83 (2004), pp.1046-105.
[131]de Llanos M, Ballesca JL, Gazquez C, Margarit E, Oliva R. High frequency of gr/gr chromosome Y deletions in consecutive oligospermic ICSI candidates. Hum Reprod.2005;2:216-20.
[132][132] Li Y, Pan KJ, Wang L, Ren J. Association of gr/gr deletion in the AZFc region of Y chromosome with male infertility: a meta-analysis. Zhonghua Nan Ke Xue.2011 Jun;17(6):546-52.
[133]Kuijper EA, Blankenstein MA, Luttikhof LJ, Roek SJ, Overbeek A, Hompes PG, et al. Frequency distribution of polymorphisms in the FSH receptor gene in infertility patients of different ethnicity. Reprod Biomed Online. 2010;20:588-93.
[134]Dobson MJ, Pearlman RE, Karaiskakis A, Spyropoulos B, Moens PB. Synaptonemal complex proteins:occurrence, epitope mapping and chromosome disjunction. Journal of Cell Science.1994;107(10):2749-2760.
[135]Yuan L, Pelttari J, Brundell E, et al. The synaptonemal complex protein SCP3 can form multistranded, cross-striated fibers in vivo. Journal of Cell Biology. 1998;142(2):331-339.
[136]Yuan L, Liu JG, Zhao J, Brundell E, Daneholt B, Hoog C. The murine SCP3 gene is required for synaptonemal complex assembly, chromosome synapsis, and male fertility. Molecular Cell.2000;5(1):73-83.
[137]Miyamoto T, Hasuike S, Yogev L, et al. Azoospermia in patients heterozygous for a mutation in SYCP3. The Lancet.2003;362(9397):1714-1719.
[138]Yan W, Ma I, Burns KH, Matzuk MM. Haploinsufficiency of kelch-like protein homolog 10 causes infertility in male mice. Proceedings of the National Academy of Sciences of the United States of America. 2004;101(20):7793-7798.
[139]Wang S, Zheng H, Esaki Y, Kelly F, Yan W. Cullin3 is a KLHL10-interacting protein preferentially expressed during late spermiogenesis. Biology of Reproduction.2006;74(1):102-108.
[140]Dieterich K, Rifo RS, Faure AK, et al. Homozygous mutation of AURKC yields large-headed polyploid spermatozoa and causes male infertility. Nature Genetics.2007;39(5):661-665.
[141]Selhub J. Homocysteine metabolism. Annu Rev Nutr.1999; 19:217-46.
[142]Martin RH. Cytogenetic determinants of male fertility. Hum Reprod Update. 2008;14:379-90.
[143]Selice R, Di Mambro A, Garolla A, Ficarra V, Iafrate M, Ferlin A, et al. Spermatogenesis in Klinefelter syndrome. J Endocrinol Invest.2010;33:789-93.
[144]Lim AS, Fong Y, Yu SL. Estimates of sperm sex chromosome disomy and diploidy rates in a 47,XXY/46,XY mosaic Klinefelter patient. Hum Genet. 1999;104:405-9.
[145]Kruse R, Guttenbach M, Shartmann B, Schubert R, van der Ven H, Schmid M, et al. Genetic counselling in a patient with XXY/XXXY/XY mosaic Klinefelter's syndrome:estimate of sex chromosome aberrations in sperm before intracytoplasmic sperm injection. Fertil Steril.1998;69:432-85.
[146]Rives N, Joly G, Machy A, Simeon N, Leclerc P, Mace B. Assessment of sex chromosome aneuploidy in sperm nuclei from 47,XXY and 46,XY/47,XXY males:comparison with fertile and infertile males with normal karyotype. Mol Hum Reprod.2000;6:107-12.
[147]Estop AM, Cieply KM, Wakim A, Feingold E. Meiotic products of two reciprocal translocations studied by multicolor fluorescence in situ hybridization. Cytogenet Cell Genet.1998;83:193-8.
[148]Hall H, Hunt P, Hassold T.2006. Meiosis and sex chromosome aneuploidy: How meiotic errors cause aneuploidy; how aneuploidy causes meiotic errors. Curr Opin Genet Dev 16:323-329.
[149]Thomas NS, Hassold TJ.2003. Aberrant recombination and the origin of Klinefelter syndrome. Hum Reprod Update 9:309-317.
[150]Robinson DO, Jacobs PA.1999. The origin of the extra Y chromosome in males with a 47,XYY karyotype. Hum Mol Genet 8:2205-2209.
[151]Jacobs P, Dalton P, James R, Mosse K, Power M, Robinson D, Skuse D.1997. Turner syndrome:A cytogenetic and molecular study. Ann Hum Genet 61: 471-483.
[152]P.S Burgoyne. The role of sex chromosomes in mammalian germ cell differentiation Ann Biol Anim Biochim Biophys,18 (1978), pp.317-325.
[153]J Forejt.X-Y involvement in male sterility caused by autosome translocationsa hypothesis. P.G Crosignani, B.L Rubin, M Fraccaro (Eds.), Genetic control of gamete production and function. (Proc Serono Clinical Colloquia on Reproduction No.3), Academic Press, New York (1982), pp.261-273.
[154]Dada R, Gupta NP, Kucheria K. Semen cryopreservation in men with AZFc microdeletion. Clin Genet.2003;64:74-5.
[155]Hopps CV, Mielnik A, Goldstein M, Palermo GD, Rosenwakes Z, Schlegel PN. Detection of sperm in men with Y chromosome microdeletions of the AZFa, AZFb and AZFc regions. Hum Repord.2003 Aug; 18(8):1660-5.
[156]Shi YC, Cui YX, Wei L, Zhou YC, Shao Y, Xia XY, Shang XJ, Zhu WM, Huang YF. AZF microdeletions on the Y chromosome in infertile Chinese men:a five-year retrospective analysis. Zhonghua Nan Ke Xue.2010 Apr;16(4):314-9.
[157]Dai RL, Sun LK, Yang X, Li LL, Zhu HB, Liu RZ. Expansion and de novo occurrence of Y chromosome microdeletions occurring via natural vertical transmission in northeastern China. J Int Med Res.2012;40(3):1182-91.
[158]World Health Organization (WHO). WHO Laboratory Manual for the Examination of Human Semen and Semen-Cervical Mucus Interaction.4th ed. Cambridge, United Kingdom:Cambridge University Press; 1999.
[159]Shaffer LG, Slovak ML, Campbell LJ:ISCN 2009:an international system for human cytogenetic nomenclature (2009). Switzerland: Karger,2009,16-31.
[160]Simoni M, Bakker E, Krausz C. EAA/EMQN best practice guidelines for molecular diagnosis of y-chromosomal microdeletions. State of the art 2004. Int J Androl.2004,27(4):240-9.
[161]Zhou-Cun A, Yang Y, Zhang SZ, Zhang W, Lin L. Chromosomal abnormality and Y chromosome microdeletion in Chinese patients with azoospermia or severe oligozoospermia. Yi Chuan Xue Bao.2006 Feb;33(2):111-6.
[162]Maiburg M, Repping S, Giltay J. The genetic origin of Klinefelter syndrome and its effect on spermatogenesis. Fertil Steril 2012; 98(2):253-60.
[163]Ghorbel M, Gargouri Baklouti S, Ben Abdallah F Zribi N, Cherif M, Keskes R, Chakroun N, Sellami A, Belguith N, Kamoun H, et al. Chromosomal defects in infertile men with poor semen quality. J Assist Reprod Genet 2012;29(5):451-6.
[164]Ravel C,Chantot-Bastaraud S, Cretet J. Klinefelter syndrome:spermatogenesis and quality of gametes. Gynecol Obstet Fertil 2011;39(9):525-8.
[165]P.S Burgoyne. The role of sex chromosomes in mammalian germ cell differentiation Ann Biol Anim Biochim Biophys,18 (1978), pp.317-325
[166]Fullerton G, Hamilton M, Maheshwari A. Should non-mosaic Klinefelter syndrome men be labelled as infertile in 2009?. Hum Reprod 2010;25(3):588-97.
[167]Kliesch S, Zitzmann M, Behre HM. Fertility in patients with Klinefelter syndrome (47,XXY).Urologe A 2011;50(1):26-32.
[168]Houk CP, Rogol A, Lee PA. Fertility in men with Klinefleter syndrome. Pediatr Endocrinol Rev 2010; 8 Suppl 1:182-6.
[169]Ulug U, Bener F, Akman MA, Bahceci M. Partners of men with Klinefelter syndrome can benefit from assisted reproductive technologies. Fertil Steril. 2003 Oct;80(4):903-6.
[170]Sokol RZ. It's not all about the testes: medical issues in Klinefelter patients. Fertil Steril.2012 Aug;98(2):261-5.
[171]Mehta A, Paduch DA. Klinefelter syndrome: an argument for early aggressive hormonal and fertility management. Fertil Steril.2012 Aug;98(2):274-83.
[172]Uccellatore F, Padova G, Squatrito S. Reproductive hormone studies in three subjects with a Robertsonian translocation. J Endocrinol Invest.1983 Dec;6(6):479-84.
[173]J Forejt.X-Y involvement in male sterility caused by autosome translocationsa hypothesis P.G Crosignani, B.L Rubin, M Fraccaro (Eds.), Genetic control of gamete production and function. (Proc Serono Clinical Colloquia on Reproduction No.3), Academic Press, New York (1982), pp.261-273
[174]Dong Y, Du RC, Jiang YT, Wu J, Li LL, Liu RZ. Impact of chromosomal translocations on male infertility, semen quality, testicular volume and reproductive hormone levels. J Int Med Res.2012;40(6):2274-83.
[175]Matsuda T, Nonomura M, Yamamoto S, Hayashi K, Yoshida O. Sperm morphology in subfertile carriers of autosomal translocations. Int J Fertil1991;36(3):178-82.
[176]Yoshida A, Miura K, Shirai M. Cytogenetic survey of 1,007 infertile males.Urol Int1997;58(3):166-76.
[177]Brahem S, Elghezal H, Ghedir H, Landolsi H, Amara A, Ibala S, Gribaa M, Saad A,Mehdi M. Cytogenetic and molecular aspects of absolute teratozoospermia:comparison between polymorphic and monomorphic forms. Urology 2011;78(6):1313-9.
[178]Keymolen K, Staessen C, Verpoest W, Michiels A, Bonduelle M, Haentjens P, Vanderelst J, Liebaers I. A proposal for reproductive counselling in carriers of Robertsonian translocations:10 years of experience with preimplantation genetic diagnosis. Hum Reprod.2009 Sep;24(9):2365-71.
[179]Anton E, Vidal F, Blanco J. Interchromosomal effect analyses by sperm FISH: incidence and distribution among reorganization carriers. Syst Biol Reprod Med.2011 Dec;57(6):268-78.
[180]Chang EM, Han JE, Kwak IP, Lee WS, Yoon TK, Shim SH. Preimplantation genetic diagnosis for couples with a Robertsonian translocation:practical information for genetic counseling. J Assist Reprod Genet.2012 Jan;29(1):67-75.
[181]Zhao H, Xu J, Zhang H, Sun J, Sun Y, Wang Z, Liu J, Ding Q, Lu S, Shi R, You L, Qin Y, Zhao X, Lin X, Li X, Feng J, Wang L, Trent JM, Xu C, Gao Y, Zhang B, Gao X, Hu J, Chen H, Li G, Zhao J, Zou S, Jiang H, Hao C, Zhao Y, Ma J, Zheng SL, Chen ZJ.A genome-wide association study reveals that variants within the HLA region are associated with risk for nonobstructive azoospermia. Am J Hum Genet.2012 May 4;90(5):900-6.
[182]Teng YN, Chang YP, Tseng JT, Kuo PH, Lee IW, Lee MS, Kuo PL. A single-nucleotide polymorphism of the DAZL gene promoter confers susceptibility to spermatogenic failure in the Taiwanese Han. Hum Reprod 2012;27(9):2857-65.
[183]Jensen TK, Andersson AM, Hjollund NH, Scheike T, Kolstad H, Giwercman A, Henriksen TB, Ernst E, Bonde JP, Olsen J, McNeilly A, Groome NP, Skakkebaek NE.Inhibin B as a serum marker of spermatogenesis:correlation to differences in sperm concentration and follicle-stimulating hormone levels. A study of 349 Danish men. J Clin Endocrinol Metab.1997 Dec;82(12):4059-63.
[184]Bergmann M, Behre HM, Nieschlag E.Serum FSH and testicular morphology in male infertility. Clin Endocrinol (Oxf).1994 Jan;40(1):133-6.
[185]Arai T, Kitahara S, Horiuchi S, Sumi S, Yoshida K. Relationship of testicular volume to semen profiles and serum hormone concentrations in infertile Japanese males. Int J Fertil Womens Med1998;43(1):40-7.
[186]Bayasgalan G, Naranbat D, Radnaabazar J, Lhagvasuren T, Rowe PJ. Male infertility, risk factors in Mongolian men. Asian J Androl 2004;6(4):305-11.
[187]Bak CW, Byun JS, Lee JH, Park JH, Lee KA, Shim SH. Clinical and social characteristics of Korean men with Klinefelter syndrome Int J Urol. 2012;19(5):443-9.
[188]Aribarg A, Kenkeerati W, Vorapaiboonsak V, Leepipatpaiboon S, Farley TM. Testicular volume, semen profile and serum hormone levels in fertile Thai males. Int J Androl 1986;9(3):170-80.
[189]de Gouveia Brazao CA, Pierik FH, Erenpreiss Y, de Jong FH, Dohle GR, Weber RF. The effect of cryptorchidism on inhibin B in a subfertile population. Clin Endocrinol (Oxf) 2003;59(1):136-41.
[190]Hammar M, Berg AA. Impaired Leydig cell function in vitro in testicular tissue from human males with "Sertoli cell only" syndrome. Andrologia.1985 Jan-Feb;17(1):37-41.
[191]Andersson AM, J(?)rgensen N, Frydelund-Larsen L, Rajpert-De Meyts E, Skakkebaek NE. Impaired Leydig cell function in infertile men:a study of 357 idiopathic infertile men and 318 proven fertile controls. J Clin Endocrinol Metab.2004 Jul;89(7):3161-7.
[192]Holm M, Rajpert-De Meyts E, Andersson AM, Skakkebaek NE. Leydig cell micronodules are a common finding in testicular biopsies from men with impaired spermatogenesis and are associated with decreased testosterone/LH ratio. J Pathol.2003 Mar;199(3):378-86.
[193]Kyriacou C, Kottaridis PD, Eliahoo J, McKeag N, Bomford J, McGarrigle HH, Linch DC, Mackinnon S, Chatterjee R. Germ cell damage and Leydig cell insufficiency in recipients of nonmyeloablative transplantation for haematological malignancies. Bone Marrow Transplant.2003 Jan;31(1):45-50.
[194]Wu O, Wang H, Liu YL, Xu Y, Wang P, Shi HJ, Feng Y. Sequence tagged sites of AZFc microdeletion in Chinese Han population. Zhonghua Nan Ke Xue.2011 May;17(5):391-5.
[195]Nie ZY, Wu HF, Zhang N, Guo LN, Zhao SY, Zhen XL, Lu CT. Influence of male age on the outcome of conventional IVF-ET. Zhonghua Nan Ke Xue 2012;18(3):248-52.
[196]Cui YQ, Gao ES, Zhou WJ, Wu JQ, Yuan W. Association between age and quality of semen in Chinese males with normal fertility. Zhonghua Liu Xing Bing Xue Za Zhi 2009; 30(9):899-902.
[197]Sartorius GA, Nieschlag E. Paternal age and reproduction. Hum Reprod Update 2010;16(1):65-7.
[198]Liu Y, Kong XD, Wu QH, Li G, Song L, Sun YP. Karyotype analysis in large-sample infertile couples living in Central China:a study of 14965 couples. J Assist Reprod Genet.2013 Apr;30(4):547-53.
[199]Samli H, Samli MM, Solak M, Imirzalioglu N.Genetic anomalies detected in patients with non-obstructive azoospermia and oligozoospermia. Arch Androl.2006 Jul-Aug;52(4):263-7
[200]Ng PP, Tang MH, Lau ET, Ng LK, Ng EH, Tam PC, Yeung WS, Ho PC.Chromosomal anomalies and Y-microdeletions among Chinese subfertile men in Hong Kong. Hong Kong Med J.2009 Feb;15(1):31-8.
[201]Ghorbel M, Gargouri Baklouti S, Ben Abdallah F, Zribi N, Cherif M, Keskes R, Chakroun N, Sellami A, Belguith N, Kamoun H, Fakhfakh F, Ammar-Keskes L. Chromosomal defects in infertile men with poor semen quality. J Assist Reprod Genet.2012 May;29(5):451-6.
[202]Fu L, Xiong DK, Ding XP, Li C, Zhang LY, Ding M, Nie SS, Quan Q. Genetic screening for chromosomal abnormalities and Y chromosome microdeletions in Chinese infertile men. J Assist Reprod Genet.2012 Jun;29(6):521-7.
[203]Dul EC, van Echten-Arends J, Groen H, Dijkhuizen T, Land JA, van Ravenswaaij-Arts CM. Chromosomal abnormalities in azoospermic and non-azoospermic infertile men:numbers needed to be screened to prevent adverse pregnancy outcomes. Hum Reprod.2012 Sep;27(9):2850-6.
[204]Alhalabi M, Kenj M, Monem F, Mahayri Z, Abou Alchamat G, Madania A.High prevalence of genetic abnormalities in Middle Eastern patients with idiopathic non-obstructive azoospermia. J Assist Reprod Genet.2013 Jun;30(6):799-805.
[205]Pylyp LY, Spinenko LO, Verhoglyad NV, Zukin VD.Chromosomal abnormalities in patients with oligozoospermia and non-obstructive azoospermia. J Assist Reprod Genet.2013 Jun;30(5):729-32.