染色体多态性对男性生精能力及生育结局的研究
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摘要
目的探讨染色体多态性对男性生精能力和生育结局的影响。方法选择3 203例男性不育者(不育组)和4 893例捐精初筛合格者(捐精组)进行回顾性队列研究,其中根据精液精子数量将不孕组患者分为精子正常组、少精子症组、无精子症组。检查并比较各组的精液常规、染色体核型、Y染色体微缺失。对有多态性的捐精者和患者进行随访,了解他们的生育结局。结果不育组和捐精组多态性发生率分别为4.62%和3.78%,差异无统计学意义(P>0.05)。不育组的Y异染色质长度减少(Yqh-)发生率(0.59%)高于捐精组(0.27%),差异有统计学意义(P=0.022),且随着精子数量减少Yqh-发生率明显增加(精子数量正常组为0.15%,少精子症组为0.22%,无精子症组为0.99%),差异有统计学意义(精子正常组与无精子症组P=0.033;少精子症组与无精子症组P=0.027)。携带有Yqh-的患者Y染色体微缺失检出率为56.25%(9/16),显著高于其它类型人群(P<0.001)。不育组中弱精子者和畸形精子者的多态性发生率分别为3.92%、3.96%,同捐精组(3.78%)相比,差异无统计学意义(P>0.05)。随访捐精组和不育组有多态性人群的配偶,结果其自然流产率分别为6.25%(3/48)和6.67%(2/30),差异无统计学意义(P>0.05),且无1例发生子代出生缺陷。结论除Yqh-部分伴随无精子因子(AZF)缺失可导致精子发生障碍,使男性生育力下降,其它类型多态对男性生育无明显影响。
Objective To investigate the effect of chromosome polymorphism on the male spermatogenesis and reproductive outcomes. Methods Totally 3 203 cases of male(infertile group), who were divided into normozoospermia group, aligozoospermia group, azoospermia group according to the sperm count of semen analysis, and 4 893 cases of donor(donor group) were involved the study. Semen analysis, karyotype analysis, and Y chromosome microdeletion test were compared between the groups. The reproductive outcomes of sperm donors and infertile patients were investigated. Results The incidence of polymorphism in infertile group and donor group was 4.62% and 3.78% respectively, and the difference was not statistically significant. The incidence of Yqh-in infertile patients increased significantly with the decrease of sperm count(0.15% in normozoospermia group, 0.22% in aligozoospermia group, 0.99% in azoospermia group), and the difference was statistically significant(P=0.033, compared between normozoospermia group and azoospermia group; P=0.027, compared between aligozoospermia group and azoospermia group), the rate of Y chromosome microdeletion in group C with Yqh-was 56.25%(9/16), significantly higher than that of other groups(P<0.05). The incidence of polymorphism in the asthenozoospermia group and teratozoospermia group was 3.92% and 3.96%, respectively, and the difference was not statistically significant(P>0.05). Follow-up investigation found that the spontaneous abortion rate was 6.25%(3/48) and 6.67%(2/30) in people with polymorphic of donor group and infertile group respectively, no statistical significance(P>0.05), and no child birth defects were observed. Conclusion Part with azoospermia factor(AZF) microdeletion in Yqh-may lead to spermatogenesis, and other types of polymorphism have no obvious effect on male fertility.
Objective To investigate the effect of chromosome polymorphism on the male spermatogenesis and reproductive outcomes. Methods Totally 3 203 cases of male(infertile group), who were divided into normozoospermia group, aligozoospermia group, azoospermia group according to the sperm count of semen analysis, and 4 893 cases of donor(donor group) were involved the study. Semen analysis, karyotype analysis, and Y chromosome microdeletion test were compared between the groups. The reproductive outcomes of sperm donors and infertile patients were investigated. Results The incidence of polymorphism in infertile group and donor group was 4.62% and 3.78% respectively, and the difference was not statistically significant. The incidence of Yqh-in infertile patients increased significantly with the decrease of sperm count(0.15% in normozoospermia group, 0.22% in aligozoospermia group, 0.99% in azoospermia group), and the difference was statistically significant(P=0.033, compared between normozoospermia group and azoospermia group; P=0.027, compared between aligozoospermia group and azoospermia group), the rate of Y chromosome microdeletion in group C with Yqh-was 56.25%(9/16), significantly higher than that of other groups(P<0.05). The incidence of polymorphism in the asthenozoospermia group and teratozoospermia group was 3.92% and 3.96%, respectively, and the difference was not statistically significant(P>0.05). Follow-up investigation found that the spontaneous abortion rate was 6.25%(3/48) and 6.67%(2/30) in people with polymorphic of donor group and infertile group respectively, no statistical significance(P>0.05), and no child birth defects were observed. Conclusion Part with azoospermia factor(AZF) microdeletion in Yqh-may lead to spermatogenesis, and other types of polymorphism have no obvious effect on male fertility.
引文
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[4]李宏军.辅助生殖技术前应重视男性不育患者的常规处理[J].中华生殖与避孕杂志,2017,37(4):343-346.DOI:10.3760/cma.j.issn.2096-2916.2017.04.0343.
[5]Babu A,Agarwal AK,Verma RS.A new approach in recognition of heterochromatic regions of human chromosomes by means of restriction endonucleases[J].Am J Hum Genet,1988,42(1):60-65.
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[8]朱晓斌,李铮,郭安亮,等.Y染色体微缺失父子间垂直遗传分析[J].中华医学遗传学杂志,2007,24(2):203-205.
[9]Chatziparasidou A,Christoforidis N,Samolada G,et al.Sperm aneuploidy in infertile male patients:a systematic review of the literature[J].Andrologia,2015,47(8):847-860.DOI:10.1111/and.12362.
[10]《男性生殖遗传学检查专家共识》编写组,商学军,陈亮,等.男性生殖遗传学检查专家共识[J].中华男科学杂志,2015,21(12):1138-1142.DOI:10.13263/j.cnki.nja.2015.12.017.
[11]Turki RF,Mourad A,Banni HA,et al.Associations of recurrent miscarriages with chromosomal abnormalities,thrombophilia allelic polymorphisms and/or consanguinity in Saudi Arabia[J].BMC Med Genet,2016,17(1):69.DOI:10.1186/s12881-016-0331-1.
[12]Madon PF,Athalye AS,Parikh FR.Polymorphic variants on chromosomes probably play a significant role in infertility[J].Reprod Biomed Online,2005,11(6):726-732.
[13]Morales R,LledóB,Ortiz JA,et al.Chromosomal polymorphic variants increase aneuploidies in male gametes and embryos[J].Syst Biol Reprod Med,2016,62(5):1.DOI:10.1080/19396368.2016.1212949.
[14]Dobigny G,Brittondavidian J,Robinson TJ.Chromosomal polymorphism in mammals:an evolutionary perspective[J].Biol Rev,2017,92(1):1.DOI:10.1111/brv.12213.
[15]Mierla D,Stoian V.Chromosomal polymorphisms involved in reproductive failure in the romanian population[J].Balkan J Med Genet,2013,15(2):23.DOI:10.2478/bjmg-2013-0003.
[16]Palacios-Gimenez OM,Dias GB,de Lima LG,et al.High-throughput analysis of the satellitome revealed enormous diversity of satellite DNAs in the neo-Y chromosome of the cricket Eneoptera surinamensis[J].Sci Rep,2017,7(1):6422.DOI:10.1038/s41598-017-06822-8.
[17]戴小凡,赵菁,刘凌云,等.染色体多态性对男性精液质量的影响[J].中国妇幼保健,2014,29(4):567-568.
[18]Hong Y,Zhou YW,Tao J,et al.Do polymorphic variants of chromosomes affect the outcome of in vitro fertilization and embryo transfer treatment?[J].Hum Reprod,2011,26(4):933-940.DOI:10.1093/humrep/deq333.
[19]Luna M,Cervantes E,Vela G,et al.Polymorphic variant karyotypes are not innocuous to IVF outcome[J].Fertil Steril,2012,98(3):S277.DOI:10.1016/j.fertnstert.2012.07.1007.
[20]肖卓妮,徐望明,杨菁.Y染色体多态性对体外受精-胚胎移植妊娠结局的影响[J].中华临床医师杂志:电子版,2012,6(18):150-152.DOI:10.3877/cma.j.issn.1674-0785.2012.18.056.
[21]松迪,印惠荣,张慧琴,等.染色体多态性不影响体外受精胚胎移植技术的生殖结局[J].第二军医大学学报,2017,38(7):836-841.
[22]Ran C,Ma Y,Ying N,et al.Chromosomal polymorphisms are associated with female infertility and adverse reproductive outcomes after infertility treatment:a 7-year retrospective study[J].Reprod Biomed Online,2017,35(1):72-80.DOI:10.1016/j.rbmo.2017.03.022.
[23]周丹妮,李赛姣,杨菁,等.男性染色体多态性对精子质量及体外受精/卵胞质内单精子显微注射结局的影响[J].中华生殖与避孕杂志,2017,37(10):797-802.DOI:10.3760/cma.j.issn.2096-2916.2017.10.004.
[24]汪小波,胡洪亮,朱勇,等.染色体多态性对男性生育力的影响//中华医学会生殖医学分会人类精子库管理学组第三届年会全国男性生殖医学和精子库管理新进展第四次研讨会论文汇编[C],深圳:中华医学会,2012:305-306.
[2]Punab M,Poolamets O,Paju P,et al.causes of male infertility:a 9-year prospective monocentre study on 1 737 patients with reduced total sperm counts[J].Hum Reprod,2017,32(1):18-31.DOI:10.1093/humrep/dew284.
[3]Vaiman D.Genetic regulation of recurrent spontaneous abortion in humans[J].Biomed J,2015,38(1):11.DOI:10.4103/2319-4170.133777.
[4]李宏军.辅助生殖技术前应重视男性不育患者的常规处理[J].中华生殖与避孕杂志,2017,37(4):343-346.DOI:10.3760/cma.j.issn.2096-2916.2017.04.0343.
[5]Babu A,Agarwal AK,Verma RS.A new approach in recognition of heterochromatic regions of human chromosomes by means of restriction endonucleases[J].Am J Hum Genet,1988,42(1):60-65.
[6]Brothman AR,Schneider NR,Saikevych I,et al.Cytogenetic heteromorphisms:survey results and reporting practices of giemsaband regions that we have pondered for years[J].Arch Pathol Lab Med,2006,130(7):947-949.DOI:10.1043/1543-2165(2006)130[947:CHSRAR]2.0.CO;2.
[7]中华人民共和国卫生部.人类辅助生殖技术和人类精子库伦理原则[J].中国生育健康杂志,2004,15(2):72-74.
[8]朱晓斌,李铮,郭安亮,等.Y染色体微缺失父子间垂直遗传分析[J].中华医学遗传学杂志,2007,24(2):203-205.
[9]Chatziparasidou A,Christoforidis N,Samolada G,et al.Sperm aneuploidy in infertile male patients:a systematic review of the literature[J].Andrologia,2015,47(8):847-860.DOI:10.1111/and.12362.
[10]《男性生殖遗传学检查专家共识》编写组,商学军,陈亮,等.男性生殖遗传学检查专家共识[J].中华男科学杂志,2015,21(12):1138-1142.DOI:10.13263/j.cnki.nja.2015.12.017.
[11]Turki RF,Mourad A,Banni HA,et al.Associations of recurrent miscarriages with chromosomal abnormalities,thrombophilia allelic polymorphisms and/or consanguinity in Saudi Arabia[J].BMC Med Genet,2016,17(1):69.DOI:10.1186/s12881-016-0331-1.
[12]Madon PF,Athalye AS,Parikh FR.Polymorphic variants on chromosomes probably play a significant role in infertility[J].Reprod Biomed Online,2005,11(6):726-732.
[13]Morales R,LledóB,Ortiz JA,et al.Chromosomal polymorphic variants increase aneuploidies in male gametes and embryos[J].Syst Biol Reprod Med,2016,62(5):1.DOI:10.1080/19396368.2016.1212949.
[14]Dobigny G,Brittondavidian J,Robinson TJ.Chromosomal polymorphism in mammals:an evolutionary perspective[J].Biol Rev,2017,92(1):1.DOI:10.1111/brv.12213.
[15]Mierla D,Stoian V.Chromosomal polymorphisms involved in reproductive failure in the romanian population[J].Balkan J Med Genet,2013,15(2):23.DOI:10.2478/bjmg-2013-0003.
[16]Palacios-Gimenez OM,Dias GB,de Lima LG,et al.High-throughput analysis of the satellitome revealed enormous diversity of satellite DNAs in the neo-Y chromosome of the cricket Eneoptera surinamensis[J].Sci Rep,2017,7(1):6422.DOI:10.1038/s41598-017-06822-8.
[17]戴小凡,赵菁,刘凌云,等.染色体多态性对男性精液质量的影响[J].中国妇幼保健,2014,29(4):567-568.
[18]Hong Y,Zhou YW,Tao J,et al.Do polymorphic variants of chromosomes affect the outcome of in vitro fertilization and embryo transfer treatment?[J].Hum Reprod,2011,26(4):933-940.DOI:10.1093/humrep/deq333.
[19]Luna M,Cervantes E,Vela G,et al.Polymorphic variant karyotypes are not innocuous to IVF outcome[J].Fertil Steril,2012,98(3):S277.DOI:10.1016/j.fertnstert.2012.07.1007.
[20]肖卓妮,徐望明,杨菁.Y染色体多态性对体外受精-胚胎移植妊娠结局的影响[J].中华临床医师杂志:电子版,2012,6(18):150-152.DOI:10.3877/cma.j.issn.1674-0785.2012.18.056.
[21]松迪,印惠荣,张慧琴,等.染色体多态性不影响体外受精胚胎移植技术的生殖结局[J].第二军医大学学报,2017,38(7):836-841.
[22]Ran C,Ma Y,Ying N,et al.Chromosomal polymorphisms are associated with female infertility and adverse reproductive outcomes after infertility treatment:a 7-year retrospective study[J].Reprod Biomed Online,2017,35(1):72-80.DOI:10.1016/j.rbmo.2017.03.022.
[23]周丹妮,李赛姣,杨菁,等.男性染色体多态性对精子质量及体外受精/卵胞质内单精子显微注射结局的影响[J].中华生殖与避孕杂志,2017,37(10):797-802.DOI:10.3760/cma.j.issn.2096-2916.2017.10.004.
[24]汪小波,胡洪亮,朱勇,等.染色体多态性对男性生育力的影响//中华医学会生殖医学分会人类精子库管理学组第三届年会全国男性生殖医学和精子库管理新进展第四次研讨会论文汇编[C],深圳:中华医学会,2012:305-306.