早期自然流产发病原因的初步探讨
|
摘要
研究背景:
早期自然流产是一种严重影响妇女身心健康的疾病,目前尚缺乏有效的诊断和治疗的办法。其发病原因非常复杂,涉及妇产科学、遗传学、流行病学、职业医学、免疫学、血液及内分泌学等多个学科。仅仅局限在一个狭窄领域的病因学研究,难以获得对早期自然流产的全方位认识。目前国内外尚缺乏从不同角度来阐述早期自然流产发病原因的报道。
随着科技的发展,大气污染、水污染、噪声污染和电磁辐射污染已经成为人类生活环境中的四种主要污染源,但到目前为止,生活环境中的有害因素对妊娠的影响尚未得到足够的重视,没有相关的基本流行病学资料。
虽然人们早就认识到胚胎的细胞遗传学异常是早期自然流产的重要原因之一,但引起其异常的原因目前仍然不清楚。
现阶段的蛋白质研究多停留在是研究已知的蛋白质与早期自然流产关系的水平上,所能涉及的蛋白质数量非常有限。近年来迅速发展的蛋白质组学技术,高通量、高灵敏度和规模化的双向凝胶电泳结合质谱技术为我们提供了一个能够比较全面认识组织蛋白质成份的平台,可以帮助我们寻找早期自然流产特异表达的蛋白质。如果能将这些特异表达的蛋白质作为临床诊断的生物标记分子或药物开发的分子靶标,早期自然流产就有望成为可以早期诊断并治疗的疾病。
研究目的:
比较自然流产患者和正常妊娠妇女流行病学特点和蛋白质表达的差异、分析自然流产患者的绒毛染色体核型,从流行病学、蛋白质组学和细胞遗传学三个角度探讨自然流产的发病原因。
研究方法:
1.流行病学调查。问卷调查200对自然流产患者和正常足月分娩妇女在早孕期的生活环境情况,分析环境因素对妊娠的影响。
2.细胞遗传学研究。分析453例早期自然流产患者的绒毛染色体核型,研究早期自然流产的细胞遗传学特点。
3.蛋白质组学研究。采用双向凝胶电泳结合MALDI质谱分析技术,比较自然流产患者和正常妊娠妇女的绒毛组织中蛋白质表达的差异,寻找自然流产特异表达的蛋白质。
结果:
1.单因素分析显示自然流产组平均每周看电视在10小时以上,使用电脑在45小时以上、经常使用复印机、微波炉和手机的比例显著高于对照组(P＜0.05);自然流产组生活环境附近有高压线等电磁辐射装置、有排放污染气体的工厂、有持续10个月以上的噪音、孕期或孕前半年家庭或工作场所采用挥发异味的材料进行过装修的比例也显著高于对照组(P＜0.05),且随着装修异味时间的延长,发生自然流产的危险度增加(P＜0.001)。自然流产组孕期情绪紧张的比例显著高于对照组(P＜0.001),有自然流产史的比例也显著高于对照组(P＜0.001)。多因素分析显示早孕期经常使用微波炉、手机、接触装修材料散发的异味的时间超过3个月、情绪紧张以及有自然流产史等5种因素显著增加自然流产的相对危险性(P＜0.05)。
2.自然流产患者绒毛染色体核型异常率为58.04%;多次流产患者的绒毛染色体核型异常率明显高于初次流产患者(P＜0.05);绒毛染色体核型的异常绝大多数为染色体数目异常,其中16—三体最多见;早孕期生活环境中的高危因素(如:早孕期经常使用微波炉、手机、接触装修材料异味超过3个月、情绪紧张)并不增加绒毛染色体核型异常的比率。
3.在自然流产患者绒毛组织及正常妊娠的绒毛组织中共鉴定出14种差异表达的蛋白质,其中8种蛋白质在自然流产患者绒毛组织中表达下调,6种蛋白质在自然流产患者绒毛组织中表达上调。谷胱甘肽S-转移酶、氯离子细胞内通道3、雌激素17β-羟基类固醇脱氢酶、膜联蛋白Ⅰ、羟基前列腺素脱氢酶15(NAD)、组织蛋白酶和核糖体这7种蛋白质在以往的报告中与胚胎的发育有关。谷胱甘肽S-转移酶、氯离子细胞内通道3在不同组间重复出现,推测可能与自然流产有关。
结论:
1.早孕期经常使用微波炉、手机、接触装修材料散发的异味的时间超过3个月、情绪紧张和有自然流产史是早期自然流产的高危因素。
2.染色体核型异常特别是染色体数目异常是早期自然流产的重要原因,在复发性流产中更重要。早孕期生活环境中的高危因素对绒毛染色体核型没有明显影响。
3.双向凝胶电泳结合MALDI质谱分析这两项蛋白质组学技术可以用于分析早孕绒毛标本中的差异表达蛋白质。对这些标记蛋白质的进一步研究,可以为早期自然流产的发病机制、早期诊断和治疗提供重要的信息。
Background
Early spontaneous abortion is a devastating reproductive problem affecting mental and physical health of women. Many researches have sought to determine its causation and just a handful factors have been found to be associated with this disorder. The pathogenesis of spontaneous abortion is complicated, and the etiology of spontaneous abortion involves in several subjects, such as Obstetrics & Gynecology, Genetics, Epidemiology, Immunology, Hematology and Endocrinology and so on. A study limited in a narrow area will be very difficult to gain valuable information about this disease.
Objective
To investigate the etiological factors of early spontaneous abortion form the view of Epidemiology, Genetics and Proteomics, we compared the epidemiological characteristics and the differences of the express of the proteins between women undergone spontaneous abortion and who didn't undergone spontaneous abortion ; and analysis the embryonic chorionic karyotypes of abortion.
Research Method
1. Epidemiologic survey. To conduct analysis based on the survey of 200 early spontaneous abortion cases and the matched control group about the state of living environment by using multifactor Logistic regression analysis.
2. Study of Cytogenetics. Examine 453 chorionic karyotypes in early spontaneous abortion, to research the cytogenetical characteristics of this disorder.
3. Study of Proteomics. Using 2-DE combined with MALDI-TOF mass spectrum to identify the differential expressed proteins: 6 cases of early spontaneous abortion and the matched normal control were analysis by this approach.
Results
1. Five factories in living environment of first trimester were associated with risk of early spontaneous abortion significantly by multifactor analysis. They are using microwave oven and mobile phone usually, the duration of contacting abnormal smell of fitment material was more than 3 months, having emotional stress during the first trimester of pregnancy and having early spontaneous abortion history (P<0.05) .
2. There hundred thirty nine abortuses were successfully karyityped, 58.04% had chromosome aberrations. The abnormal rate of chorionic karyotype in cases of repeat early spontaneous abortion was significantly higher than that in first early spontaneous abortion cases (P<0.05) . Most of abnormal karyotypes were numerical abnormality. Some risk factories (such as using microwave oven and mobile phone usually, the duration of contacting abnormal smell of fitment material was more than 3 months, having emotional stress during the first trimester of pregnancy) in living environment during the first trimester weren't associated with chorionic karyotypes.
3. Fourteen differential expressed proteins were identified by 2-DE combined MALDI-TOF mass spectrum. Eight of these proteins showed decreased expression in chorionic tissue of early spontaneous abortion and six of these proteins showed increased expression in chorionic tissue of early spontaneous abortion. Of these differentially expressed proteins, seven were previously reported to be associated with embryo development.
Conclusion
1. Usually use microwave oven and mobile phone , contacting abnormal smell of fitment material more than 3 months, having emotional stress during the first trimester of pregnancy and having early spontaneous abortion history were risk factories for early spontaneous abortion .
2. Abnormality of the chromosomal karyotype especially the abnormality of the number of chromosome is the most important reasons in early spontaneous abortion, especially in early repeat spontaneous abortion. Chorionic karyotype wasn't influenced by some risk factories in living environment during the first trimester of pregnancy.
3. 2-DE combined with MALDI-TOF mass spectrum was improved to be able to identify the differential expression proteins in early spontaneous abortion sample. These proteins may be serving as an additional parameter for a better insight into the study of the diagnosis and treatment of early spontaneous abortion.
早期自然流产是一种严重影响妇女身心健康的疾病,目前尚缺乏有效的诊断和治疗的办法。其发病原因非常复杂,涉及妇产科学、遗传学、流行病学、职业医学、免疫学、血液及内分泌学等多个学科。仅仅局限在一个狭窄领域的病因学研究,难以获得对早期自然流产的全方位认识。目前国内外尚缺乏从不同角度来阐述早期自然流产发病原因的报道。
随着科技的发展,大气污染、水污染、噪声污染和电磁辐射污染已经成为人类生活环境中的四种主要污染源,但到目前为止,生活环境中的有害因素对妊娠的影响尚未得到足够的重视,没有相关的基本流行病学资料。
虽然人们早就认识到胚胎的细胞遗传学异常是早期自然流产的重要原因之一,但引起其异常的原因目前仍然不清楚。
现阶段的蛋白质研究多停留在是研究已知的蛋白质与早期自然流产关系的水平上,所能涉及的蛋白质数量非常有限。近年来迅速发展的蛋白质组学技术,高通量、高灵敏度和规模化的双向凝胶电泳结合质谱技术为我们提供了一个能够比较全面认识组织蛋白质成份的平台,可以帮助我们寻找早期自然流产特异表达的蛋白质。如果能将这些特异表达的蛋白质作为临床诊断的生物标记分子或药物开发的分子靶标,早期自然流产就有望成为可以早期诊断并治疗的疾病。
研究目的:
比较自然流产患者和正常妊娠妇女流行病学特点和蛋白质表达的差异、分析自然流产患者的绒毛染色体核型,从流行病学、蛋白质组学和细胞遗传学三个角度探讨自然流产的发病原因。
研究方法:
1.流行病学调查。问卷调查200对自然流产患者和正常足月分娩妇女在早孕期的生活环境情况,分析环境因素对妊娠的影响。
2.细胞遗传学研究。分析453例早期自然流产患者的绒毛染色体核型,研究早期自然流产的细胞遗传学特点。
3.蛋白质组学研究。采用双向凝胶电泳结合MALDI质谱分析技术,比较自然流产患者和正常妊娠妇女的绒毛组织中蛋白质表达的差异,寻找自然流产特异表达的蛋白质。
结果:
1.单因素分析显示自然流产组平均每周看电视在10小时以上,使用电脑在45小时以上、经常使用复印机、微波炉和手机的比例显著高于对照组(P＜0.05);自然流产组生活环境附近有高压线等电磁辐射装置、有排放污染气体的工厂、有持续10个月以上的噪音、孕期或孕前半年家庭或工作场所采用挥发异味的材料进行过装修的比例也显著高于对照组(P＜0.05),且随着装修异味时间的延长,发生自然流产的危险度增加(P＜0.001)。自然流产组孕期情绪紧张的比例显著高于对照组(P＜0.001),有自然流产史的比例也显著高于对照组(P＜0.001)。多因素分析显示早孕期经常使用微波炉、手机、接触装修材料散发的异味的时间超过3个月、情绪紧张以及有自然流产史等5种因素显著增加自然流产的相对危险性(P＜0.05)。
2.自然流产患者绒毛染色体核型异常率为58.04%;多次流产患者的绒毛染色体核型异常率明显高于初次流产患者(P＜0.05);绒毛染色体核型的异常绝大多数为染色体数目异常,其中16—三体最多见;早孕期生活环境中的高危因素(如:早孕期经常使用微波炉、手机、接触装修材料异味超过3个月、情绪紧张)并不增加绒毛染色体核型异常的比率。
3.在自然流产患者绒毛组织及正常妊娠的绒毛组织中共鉴定出14种差异表达的蛋白质,其中8种蛋白质在自然流产患者绒毛组织中表达下调,6种蛋白质在自然流产患者绒毛组织中表达上调。谷胱甘肽S-转移酶、氯离子细胞内通道3、雌激素17β-羟基类固醇脱氢酶、膜联蛋白Ⅰ、羟基前列腺素脱氢酶15(NAD)、组织蛋白酶和核糖体这7种蛋白质在以往的报告中与胚胎的发育有关。谷胱甘肽S-转移酶、氯离子细胞内通道3在不同组间重复出现,推测可能与自然流产有关。
结论:
1.早孕期经常使用微波炉、手机、接触装修材料散发的异味的时间超过3个月、情绪紧张和有自然流产史是早期自然流产的高危因素。
2.染色体核型异常特别是染色体数目异常是早期自然流产的重要原因,在复发性流产中更重要。早孕期生活环境中的高危因素对绒毛染色体核型没有明显影响。
3.双向凝胶电泳结合MALDI质谱分析这两项蛋白质组学技术可以用于分析早孕绒毛标本中的差异表达蛋白质。对这些标记蛋白质的进一步研究,可以为早期自然流产的发病机制、早期诊断和治疗提供重要的信息。
Background
Early spontaneous abortion is a devastating reproductive problem affecting mental and physical health of women. Many researches have sought to determine its causation and just a handful factors have been found to be associated with this disorder. The pathogenesis of spontaneous abortion is complicated, and the etiology of spontaneous abortion involves in several subjects, such as Obstetrics & Gynecology, Genetics, Epidemiology, Immunology, Hematology and Endocrinology and so on. A study limited in a narrow area will be very difficult to gain valuable information about this disease.
Objective
To investigate the etiological factors of early spontaneous abortion form the view of Epidemiology, Genetics and Proteomics, we compared the epidemiological characteristics and the differences of the express of the proteins between women undergone spontaneous abortion and who didn't undergone spontaneous abortion ; and analysis the embryonic chorionic karyotypes of abortion.
Research Method
1. Epidemiologic survey. To conduct analysis based on the survey of 200 early spontaneous abortion cases and the matched control group about the state of living environment by using multifactor Logistic regression analysis.
2. Study of Cytogenetics. Examine 453 chorionic karyotypes in early spontaneous abortion, to research the cytogenetical characteristics of this disorder.
3. Study of Proteomics. Using 2-DE combined with MALDI-TOF mass spectrum to identify the differential expressed proteins: 6 cases of early spontaneous abortion and the matched normal control were analysis by this approach.
Results
1. Five factories in living environment of first trimester were associated with risk of early spontaneous abortion significantly by multifactor analysis. They are using microwave oven and mobile phone usually, the duration of contacting abnormal smell of fitment material was more than 3 months, having emotional stress during the first trimester of pregnancy and having early spontaneous abortion history (P<0.05) .
2. There hundred thirty nine abortuses were successfully karyityped, 58.04% had chromosome aberrations. The abnormal rate of chorionic karyotype in cases of repeat early spontaneous abortion was significantly higher than that in first early spontaneous abortion cases (P<0.05) . Most of abnormal karyotypes were numerical abnormality. Some risk factories (such as using microwave oven and mobile phone usually, the duration of contacting abnormal smell of fitment material was more than 3 months, having emotional stress during the first trimester of pregnancy) in living environment during the first trimester weren't associated with chorionic karyotypes.
3. Fourteen differential expressed proteins were identified by 2-DE combined MALDI-TOF mass spectrum. Eight of these proteins showed decreased expression in chorionic tissue of early spontaneous abortion and six of these proteins showed increased expression in chorionic tissue of early spontaneous abortion. Of these differentially expressed proteins, seven were previously reported to be associated with embryo development.
Conclusion
1. Usually use microwave oven and mobile phone , contacting abnormal smell of fitment material more than 3 months, having emotional stress during the first trimester of pregnancy and having early spontaneous abortion history were risk factories for early spontaneous abortion .
2. Abnormality of the chromosomal karyotype especially the abnormality of the number of chromosome is the most important reasons in early spontaneous abortion, especially in early repeat spontaneous abortion. Chorionic karyotype wasn't influenced by some risk factories in living environment during the first trimester of pregnancy.
3. 2-DE combined with MALDI-TOF mass spectrum was improved to be able to identify the differential expression proteins in early spontaneous abortion sample. These proteins may be serving as an additional parameter for a better insight into the study of the diagnosis and treatment of early spontaneous abortion.
引文
1.Grimaldi S,Pasquali E,Barbatano L,et al.Exposure to a 50 Hz Electromagnetic field induces activation of the Epstein-Barr virus genome in latently infected human lymphoid cells.J Environ Pathol Toxicol Oncol,1997,16:205-207
2.张彦文.微波辐射与细胞凋亡.国外医学卫生学分册.1999,26:9-14
3.Spica V,Mucci N,Ursini,et al.Etsl oncogene induction by ELF modulated 50 MHZ rediafrequency electromagnetic field.Bioelectromagnetics,2000,21:8-18
4.黄相刚,曹兆进.电磁辐射对基因的影响.卫生毒理学杂志,2002,16(3):188-191
5.孟丽,彭瑞云.电磁辐射对内分泌的影响。中华物理医学与康复杂志,2004,26(4):251-254
6.马毓,刘兰女,杨青霞,等.电磁辐射对人体染色体结构稳定的影响.中国优生与遗传杂志,2002,10(5):18
7.Smith EM,Hammonds Ehlers M,Clark MK,et al.Occupational exposures and risk of female infertility.J Occup Environ Med,1997,39(2):138
8.王水明,王德文.电磁辐射对妊娠及子代的影响.解放军预防医学杂志,2002,20(5):385-387
9.Marcus M,McChesney R,Golden A,et al.Video display terminals and miscarriage.J Am Med Women Assoc,2000,55(2):84
10.Spica V,Mucci N,Ursini,et al.Etsl oncogene induction by ELF modulated 50 MHZ rediafrequency electromagnetic field.Bioelectromagnetics,2000,21:8-18
11.朱大明,年冀,何志辉,等.电磁辐射环境的潜在致突变水平.环境监测管理与技术,2005,17(1):19-21
12.Singh N,Rudra N,Bansal P,et al.Poly ADP ribosylation as a possible mechanism of microwave-biointeraction.Indian J Physical Pharmacol,1994,38:181-184
13.吴奇,刘俊茹,郝丽萍.不同类型移动电话的电磁辐射水平.环境与健康杂志,2002,5,19(3):199
14.许宏霞。苯及同系物对女工月经情况和妊娠结局的影响.中华误诊学杂志,2002,2(2):227-228
15.董红燕,刘君卓,陈冠英,等.甲醛对豚鼠肺巨噬细胞DNA的损伤作用.环境与健康杂志,1998,15(6):253-255
1. Boue J, Bou A, Lazar P. Retrospective and prospective epidemiological studies of 1500 karyotypes spontaneous human abortion. Teratology 1975; 12:11-26
2. Edmonds DK, Lindsay KS, Miller JF, Williamson E, Wood PJ. Early embryonic mortality in women. Fertil Steril 1982;38:447-453
3. Wilcox AJ, Weinberg CR, O'Connor JF, et al. Incidence of early loss of pregnancy. N Engl J Med 1988;319:189-194
4. Ohno M, Maeda T. Matsunobu A. A cytogenetic study of spontaneous abortions with direct analysis of chorionic villi. Obstet Gynecol 1991;77:394-398
5. Jacobs PA, Hassold T. Chromosome abnormalities: origin and etiology in abortions and livebirths. In: Vogel F, Sperling K, eds. Human Genetics. Berlin: Springer-Verlag; 1987:233-244
6. Neilson J, Wohert M. Chromosome abnormalities found among 34910 newborn children: results from a 13-years incidence study in Arhus, Denmark. Hum Genet 1991 ;87:81-83
7. Stephenson MD, Awartani KA, Robinson WP. Cytogenetic analysis of miscarriage from couples with recurrent miscarriage: a case-control study. Hum Reprod 2002; 17:446-451
8. Golbus MJ: Chromosome aberrations and mammalian reproduction. In Mastroianni L, Biggers J, Sadler W(eds):Fertilization and Embryonic Development in vitro. New York, Plenum Press, 1981.
9. Sugiura-Ogasawara M, Ozaki Y, Sato T, Suzumori N, Suzumori K. Poor prognosis of recurrent aborters with either maternal or paternal reciprocal translocations. Fertil Steril 2004;81:367-373
10. Goddijn M, Joosten JH, Knegt AC, et al. Clinical relevance of diagnosis structural chromosome abnormalities in couples with repeatd miscarriage. Hum Reprod 2004; 19:1013-1017
1.Bakhtiar R,Nelson RW.Electrospray ionization and matrix-assisted laser desorption ionization mass spectrometry.Emerging technologies in biomedical sciences.Biochem Pharmacol.2000;59:891-905.
2.Szallasi Z.Bioinformatics.Gene expression patterns and cancer.Nat Biotechnol.1998;16:1292-1293.
3.Lieshout EM,Knapen MF,Lange WP,Steegers EA,Peters WH Localization of glutathione S-transferases alpha and pi in human embryonic tissues at 8 weeks gestational age.Hum Reprod.1998May;13(5):1380-6.
4.Clarson LH,Greenwood SL,Mylona P,Sibley CP.Inwardly rectifying K(+) current and differentiation of human placental cytotrophoblast cells in culture.Placenta.2001 Apr;22(4):328-36.
5.Momoyo Sonoda,Fujio Okamoto,Hiroshi Kajiya Amino Acid-Permeable Anion Channels in Early Mouse Embryos and Their Possible Effects on Cleavagel.BIOLOGY OF REPRODUCTION 2003 68,947-953
6.Jarabak J,Adams JA,Williams-Ashman HG,et el.Purification of 17beta-hydroxysteroid dehydrogenase of human placenta and studies on its transhydrogenase function.J Biol Chem,1962,237:345-357
7.Luu-The V,Dufort I,Pelletier G,et al.Type 5 17beta-hydroxysteroid dehydrogenase:its role in the formation of androgens in women.Mol Cell Endocirinol 2001,171:77-82
8.RaynalP,PollardHB.Annexin:the problem of assessing the biological role for gene family of multifunctional calcium and phospholipid-bind-ingproteins.BiochemBiophysActa,1994,1147:63-93.
9.Sun M,Liu Y,Gibb W.Distribution of annexin I and II in term human fetal membranes,deciduas and placenta.Placenta.1996 Mar-Apr;17(2-3):181-4.
10.周升,符史干,沈行良 一氧化氮合酶在心血管内皮细胞中表达的调控中国热带医学,2006;6:697-699
11.钱卫平,谭玉梅,宋丹等.1280例自然流产患者的细胞遗传学分析.中南大学学报(医学版),2005,30:258-260
12.Eber SW,Pekrun A,Bardosi A,et al.Triosephosphate isomerase deficiency:haemolytic anaemia, myopathy with altered mitochondria and mental retardation due to a new variant with accelerated enzyme catabolism and diminished specific activity. Eur J Pediatr ,1991,150:761-766
13. Smith WL, Dewitt DL Prostaglandin endoperoxideHsynthases-1 and -2. Adv Immunol 1996, 62:167-215
14. Kelly RW.Inflammatory mediators and parturition. Rev Reprod 1996, 1:89-96
15. Olofsson JI, Leung PC Prostaglandins and their receptors: implications for ovarian physiology. Biol Signals 1996 ;5:90-100
16. Lupulescu A Prostaglandins, their inhibitors and cancer. Prostaglandins Leukotrienes Essent Fatty Acids 1996 ;54:83-94
17. Vadillo-Ortega F, Beltran J, Mateo H, Monozon F Phospholipase A2 and premature membrane rupture. Ginecol Obstet Mex 1994; 62:143-145
18. Mitchell M, Bibby J, Hicks B, Turnbull A Specific production of prostaglandins E2 by human amnion in vitro. Prostaglandins 1978 15:377-382
19. Okazaki T, Casey M, Okita JR, MacDonald P, Johnston J Initiation of parturition Ⅻ. Biosynthesis and metabolism of prostaglandins in human fetal membranes and uterine deciduas. Am J Obstet Gynecol 1981; 139:373-381
20. Okita RT, Okita JR Prostaglandin-metabolizing enzymes during pregnancy: characterization of NAD1-dependent prostaglandin dehydrogenase, carbonyl reductase, and cytochrome P450-dependent prostaglandin V-hydroxylase. Crit Rev Biochem Mol Biol 1996 31:101-126
21. Ensor CM, Tai HH 15-hydroxyprostaglandin dehydrogenase. J Lipid Mediat Cell Signal 1995 12:313-319 1983
22. Krook M, Marekov L, Jo¨rnvall HPurification and structural characterization of placental NAD1-linked 15-hydroxyprostaglandin dehydrogenase. The primary structure reveals the enzyme to belong to the short-chain alcohol dehydrogenase family. Biochemistry 1990; 29:738-743
23. Erwich JJHM, Keirse MJNC Placental localization of 15-hydroxy-prostaglandin dehydrogenase in early pregnancy and term pregnancy. Placenta 1992 ; 13:223-229
24. Kelly RW Pregnancy maintenance and parturition: the role of prostaglandin in manipulating the immune and inflammatory response. Endocr Rev 1994; 15:684-706
25. Sangha RK, Walton JC, Ensor CM, Tai HH, Challis JRG Immunohistochemical localization, messenger ribonucleic acid abundance, and activity of 15-hydroxyprostaglandin dehydrogenase in placenta and fetal membranes during term and preterm labor. J Clin Endocrinol Metab 1994;78:982-989
26. Patel FA, Clifton VL, Chwalisz K, Challis JRG Steroid regulation of prostaglandin dehydrogenase activity and expression in human term placenta and chorio-decidua in relation to labor. J Clin Endocrinol Metab 1999; 84:291-299
27. Cheng L, Kelly RW, Thong KJ, Hume R, Baird DT The effects of mifepristone (RU486) on prostaglandin dehydrogenase in decidual and chorionic tissue in early pregnancy. Hum Reprod 1993; 8:705-709
28. Mckeown K. J, Challis J. R. G Regulation of 15-Hydroxy Prostaglandin Dehydrogenase by Corticotrophin-Releasing Hormone through a alcium-Dependent Pathway in Human Chorion Trophoblast. Cells, 2003; J Clin Endocrinol Metab 88: 1737-1741
29. Massa R, Marliera LN, Martorana A, etal. Intracellular localization and isoformexpression of the voltage dependendation channel(VDAC)in normal and dystrophic skeletal muscle. Muscle Res Cell Motil,2000,21(5):433 442.
30. Douglas CW. Mitochondrial diseases in man and mouse. Science, 1999,283:1482-1488.
31. Zamzami N, Hirsch T, Dallaporta B, et al. Mitochondrial implicationin accidental and programmed cell death: apoptosisan necrosis. Bioenergetics&Biomembranes, 1997,29:185-193
32. Green DR, Reed JC. Mitochondria and apoptosis. Science 1998,281(5318): 1309 1312.
33. Susin SS, Earnshaw WC. Apoptosis: Acellular poison cupboard . Nature, 1999;397:387 389.
34. Liu X, Kim CN, Yang J, etal. Induction of apoptotic program in cell free extracts: requirement fo dATP and cytochromec. Cell, 1996; 86 :147- 157.
35. Gross A, McDnnell JM, Korsmeyer SJ. Bcl 2 family members an Themitochondria in apoptosis. Genes&Development, 1999; 13:1899- 1911.
36. Shimizu S, Narita M, Tsujimoto Y. Bcl 2 family proteins regulat the release of apoptogenic cytochrome C by themitochondria channel VDAC. Nature, 1999, 399:483-487.
37. Afonso S, Romagnanol L, Babiarz B. Expression of cathepsin proteinase by mouse trophoblaetin in vivo and in vitro.J Dev Dyn 1999,216:374-84
38.王安明 陈士岭 邢福祺等。组织蛋白酶B和L在早期妊娠绒毛及蜕膜中的表达.第一军医大学学报,2005;25:1365-1368
39.杨帆,刘卫平.核糖体蛋白基因及其与人类疾病的研究进展.临床与实验病理学杂志J Clin Exp Pathol 2005 Jun;20(3):354-356
1.Sweeney AM,Meyer MR,Aarons JH,Mills JL,LaPorte RE:Evaluation of methods for the prospective identification of early fetal losses in environmental epidemiology studies.Am J Epidemiol 127:843,1988
2.Edmonds DK,Lindsay KS,Miller JF,Williamson E,Wood PJ.Early embryonic mortality in women.Fertil Steril 1982;38:447-453
3.Alberman E:The epidemiology of repeated abortion.In Beard RW,Sharp F(eds):Early Pregnancy Loss:Mechanisms and Treatment.London,RCOG;1988,P9
4.Leridon H:Human Fertility:The basic Components.Chicago,University of Chicago Press,1977
5.Boue J,Bou A,Lazar R Retrospective and prospective epidemiological studies of 1500 karyotyped spontaneous human abortion.Teratology 1975;12:11-26
6.Wilcox AJ,Weinberg CR,O'Connor JF,et al.Incidence of early loss of pregnancy.N Engl J Med 1988;319:189-194
7.Ohno M,Maeda T.Matsunobu A.A cytogenetic study of spontaneous abortions with direct analysis of chorionic villi.Obstet Gynecol 1991;77:394-398
8.Jacobs PA,Hassold T.Chromosome abnormalities:origin and etiology in abortions and livebirths.In:Vogel F,Sperling K,eds.Human Genetics.Berlin:Springer-Verlag;1987:233-244
9.Simpson JL.Incidence and timing of pregnancy losses:relevance to evaluating safety of early prenatal diagnosis.Am J Med Genet 1990;35:165-173
10. Neilson J, Wohert M. Chromosome abnormalities found among 34910 newborn children: results from a 13-years incidence study in Arhus, Denmark. Hum Genet 1991;87:81-83
11. Hassold T, Chiu D. Maternal age-specific rates of numerical chromosome abnormalities with specific reference to trisomy. Hum Genet 1985;70:11-17
12. Jacobs PA, Hassold TJ. The origin of numerical chromosome abnormalities. Adv Genet 1995;33:101-133
13. Martin RH, Ko E,Rademaker A. Distribution of aneuploidy in human gametes: comparison between human sperm and oocytes. Am J Med Genet 1991;39:321-331
14. Rubio C, Gil-Salom M, Simon C, et al. Incidence of sperm chromosome abnormalities in a risk population: relationship with sperm quality and ICSI outcome. Hum Reprod 2001; 16:2084-2092
15. Stephenson MD, Awartani KA, Robinson WP. Cytogenetic analysis of miscarriage from couples with recurrent miscarriage: a case-control study. Hum Reprod 2002; 17:446-451
16. Frequency of factors associated with habitual abortion in 197 couples. Fertil Steril 1996; 66: 24—29
17. Sugiura-Ogasawara M, Ozaki Y, Sato T, Suzumori N, Suzumori K. Poor prognosis of recurrent aborters with either maternal or paternal reciprocal translocations. Fertil Steril 2004;81:367-373
18. Goddijn M, Joosten JH, Knegt AC, et al. Clinical relevance of diagnosis structural chromosome abnormalities in couples with repeated miscarriage. Hum Reprod 2004; 19:1013-1017
19. Stephenson MD, Sierra S. Reproductive outcomes in recurrent pregnancy loss associated with a potential carrier of a structural chromosome rearrangement. Fertil Steril 2006;
20. Carp H, Feldman B, Oelsner G, Schiff E. Parental karyotype and subsequent live births in recurrent miscarriage. Fertil Steril 2004;81:1296-1301
21. Bell KA, Van Deerlin PG, Haddad BR, Feinberg RF. Cytogenetic diagnosis of " normal 46,XX" Karyotypes in spontaneous abortions frequently may be misleading. Fertil Steril 1999;71:334-341
22. Lomax B, Tang S, Separovic E, et al. Comparative genomic hybridization in combination with flow cytometry improves results of cytogenetic analysis of spontaneous abortions.Am J Hum Genet. 2000;66(5):1516-21.
23. Philipp T, Feichtinger W, Van Allen MI, et al. Abnormal embryonic development diagnosed embryoscopically in early intrauterine deaths after in vitro fertilization: a preliminary report of 23 cases. Fertil Steril 2004;82:1337-1342
24.Ferro J,Martinez MC,Lara C,et al.Improved accuracy of hysteroembryoscopic biopsies for karyotyping early missed abortions.Fertil Steril 2003;80:1260-1264
25.Ober C,Aldrich CL,Chervoneva I,et al.Variation in the HLA-G promoter region influences miscarriage rates.Am J Hum Genet 2003;72:1425-1435
26.Karhukorpi J,Laitinen T,Tiilikainen AS.HLA-G polymorphism in Finnish couples with recurrent spontaneous miscarriage.Br J Obstet Gynecol 1997;104:1212-1214
27.Penzea M,Rajcy K,Gyodi E,et al.HLA-G gene polymorphism in the normal population and in recurrent spontaneous abortion in Hungary.Transplant proc 1999;31:1832-1833
28.Pfeiffer KA,Fimmers R,Engels G,et al.The HLA-G genotype is potentially associated with idiopathic recurrent spontaneous abortion.Mol Hum Reprod 2001;7:373-378
29.Aldrich CL,Stephenson MD,Karrison T,et al.HLA-G genotype and pregnancy outcome in couples with unexplained recurrent miscarriage.Hum Reprod 2001;7:1167-1172
30.Edwarda RG,Gardner RL.Choosing sex before birth.New Scientist 1968;38:218-220
31.Harper JC,Coonen E,RAmaekers FC,et al.Identification of the sex of human preimplantation embryos in two hours using an improved spreading method and fluorescent in-situ hybridization(FISH) using directly labeiied probes.Hum Reprod 1994;9:721-724
32.Munne S,Magli C,Cohen J,et al.Positive outcome after preimplantation diagnosis of aneuploidy in human embryos.Hum Reprod 1999;14:2191-2199
33.Vidal F,Gimenez C,Rubio C,et al.FISH preimplantation diagnosis of chromosome aneuploidy in recurrent pregnancy wastage.J Assist Reprod Genet 1998;15:310-313
34.Pellicer A,Rubio C,Vidal F,et al.In vitro fertilization plus preimplantation genetic diagnosis in patients with recurrent miscarriage:an analysis of chromosome abnormalities in human preimplantation embryo.Fertil Steril 1999;71:1033-1039
35.Golbus MJ:Chromosome aberrations and mammalian reproduction.In Mastroianni L,Biggers J,Sadler W(eds):Fertilization and Embryonic Development in vitro.New York,Plenum Press,1981.
36.Rocklin RE,Kitzmiller JL,Carpenter CB,et al:Maternal fetal relation.N Engl Med 295:1209,1976
37.杨珏琴等 原因不明复发性流产HLA相关性的初步研究。中国免疫学杂志,1999;15(3):135-137
38.居中亮,范丽安,陆丽华等 T辅助细胞1、2细胞因子平衡与正常妊娠及复发性流产关系的初步探讨。中华妇产科。 2000; 5 (8): 473-475.
39. Mowbray JF, Liddell H, Underwood JL,et al: Controlled trial of treatment of recurrent spontaneous abortion by immunization with paternal cells. Lancet 1:942,1985.;
40. Ito K, Obata F, Tanaka T et al., Analysis of HLA-DR types of unexplained recurrent spontaneous aborters in the Japanes population by oligonucleotide DNA typing. Tissue Antigens, 1992;40:204
41. Cauchi MN, Lim D, Young DE, et al: Treatment of recurrent aborters by immunization with paternal cells-controlled immunol 25:16,1991
42. Strassman EO:Fertili and unification of double uterus. Fertil Steril 17:165,1966
43. March CM, Isarel R: Hysteroscopic management of recurrent abortions caused by septate uterus. Am J Obste Gynecol 156:834,1987
44. Jones WS:Obsteric significance of female genital anomalies. Obstet Gynecol 10:113,1957
45. Capraro VJ, Gallego MB:Vaginal agenesis. Am J Obste Gynecol 124;98,1976
46. Cowchock S, Dehoratius RD, Wapner RJ, et al: Subclinical autoimmune disease and unexplained abortion. Am J Obste Gynecol 150:367,1984
47. Harger JH,Rabin BS, Marchese SG: The prognostic value of antinuclear antibigies in women with recurrent pregnancy losses: A prospective controlled study. Obste Gynecol 73:419,1989
48. Lubbe WF, Butler WS,palmer SJ, et al:Lupus anticoagulant in pregnancy. Br J Obste Gynaecol 91:357,1984;
49. Unander Am,Norberg R, Hahn L,et al: anticardiolipin antibodies and complement an ninety-nine women with habitual abortion. Am J Obste Gynecol 156:114,1987
50. Pedowitz P, Shelvin EL:Perinatal mortality in the unsuspected diabetic. Obste Gynaeco 9:524,1957.
51. Kalter H:Diabetes and spontaneous abortion:A historical review. Am J Obste Gynecol 156:1243,1987
52. Tupper C,Weil RJ: The problem of spontaneous abortion IX. The treatment of habital aborters by psychotherapy. Am J Obste Gynecol 83:421,1962
53. James WH: The problem of spontaneous abortion X.The efficacy of psychotherapy. Am J Obste Gynecol 85:38,1963a
54. Stray-Pedersen B, Stray- Pedersen S: Etiologic factors and subsequent reproductive performance in 195 couples with a prior history of nabitual abortion.Am J Obste Gynecol 148:140,1984
55.Kline J,Stein Z,Susser M et al:Environmental influences on early reproductive loss in a current New York City study.In Porter IH,Hook EB(eds):Human Embryonic and Fetal Death.New York,Academic Press,1980.
56.Ecker J,Laufer M,Hill JA:Measurement of embryotoxic factors is predictive of pregnancy outcome in women with a history of recurrent abortions.The Pacific Coast Fertility Soiety 40th Annual Meeting,Indian Wells.California,April 8-12,1992,Abst 0-011
57.Grimaldi S,Pasquali E,Barbatano L,et al.Exposure to a 50 Hz Electromagnetic field induces activation of the Epstein-Barr virus genome in latently infected human lymphoid cells.J Environ Pathol Toxicol Oncol,1997,16:205-207
58.张彦文。微波辐射与细胞凋亡。国外医学卫生学分册。1999,26:9-14
59.Spica V,Mucci N,Ursini,et al.Etsl oncogene induction by ELF modulated 50 MHZ rediafrequency electromagnetic field.Bioelectromagnetics,2000,21:8-18
60.黄相刚,曹兆进。电磁辐射对基因的影响。卫生毒理学杂志,2002,16(3):188-191
61.马毓,刘兰女,杨青霞,等。电磁辐射对人体染色体结构稳定的影响。中国优生与遗传杂志,2002,10(5):18
62.Smith EM,Hammonds Ehlers M,Clark MK,et al.Occupational exposures and risk of female infertility.J Occup Environ Med,1997,39(2):138
63.王水明,王德文。电磁辐射对妊娠及子代的影响。解放军预防医学杂志,2002,20(5):385-387
64.孟丽,彭瑞云。电磁辐射对内分泌的影响。中华物理医学与康复杂志,2004,26(4):251-254
65.Marcus M,McChesney R,Golden A,et al.Video display terminals and miscarriage.J Am Med Women Assoc,2000,55(2):84
66.Spica V,Mucci N,Ursini,et al.Etsl oncogene induction by ELF modulated 50 MHZ rediafrequency electromagnetic field.Bioelectromagnetics,2000,21:8-18
67.朱大明,年冀,何志辉,等。电磁辐射环境的潜在致突变水平。环境监测管理与技术,2005,17(1):19-21
68.Singh N,Rudra N,Bansal P,et al.Poly ADP ribosylation as a possible mechanism of microwave-biointeraction.Indian J Physical Pharmacol,1994,38:181-184
69.许宏霞。苯及同系物对女工月经情况和妊娠结局的影响。中华误诊学杂志,2002,2(2):227-228
70.吴奇,刘俊茹,郝丽萍。不同类型移动电话的电磁辐射水平。环境与健康杂志,2002,5,19(3):199
71.董红燕,刘君卓,陈冠英,等。甲醛对豚鼠肺巨噬细胞DNA的损伤作用。环境与健康杂志,1998,15(6):253-255
2.张彦文.微波辐射与细胞凋亡.国外医学卫生学分册.1999,26:9-14
3.Spica V,Mucci N,Ursini,et al.Etsl oncogene induction by ELF modulated 50 MHZ rediafrequency electromagnetic field.Bioelectromagnetics,2000,21:8-18
4.黄相刚,曹兆进.电磁辐射对基因的影响.卫生毒理学杂志,2002,16(3):188-191
5.孟丽,彭瑞云.电磁辐射对内分泌的影响。中华物理医学与康复杂志,2004,26(4):251-254
6.马毓,刘兰女,杨青霞,等.电磁辐射对人体染色体结构稳定的影响.中国优生与遗传杂志,2002,10(5):18
7.Smith EM,Hammonds Ehlers M,Clark MK,et al.Occupational exposures and risk of female infertility.J Occup Environ Med,1997,39(2):138
8.王水明,王德文.电磁辐射对妊娠及子代的影响.解放军预防医学杂志,2002,20(5):385-387
9.Marcus M,McChesney R,Golden A,et al.Video display terminals and miscarriage.J Am Med Women Assoc,2000,55(2):84
10.Spica V,Mucci N,Ursini,et al.Etsl oncogene induction by ELF modulated 50 MHZ rediafrequency electromagnetic field.Bioelectromagnetics,2000,21:8-18
11.朱大明,年冀,何志辉,等.电磁辐射环境的潜在致突变水平.环境监测管理与技术,2005,17(1):19-21
12.Singh N,Rudra N,Bansal P,et al.Poly ADP ribosylation as a possible mechanism of microwave-biointeraction.Indian J Physical Pharmacol,1994,38:181-184
13.吴奇,刘俊茹,郝丽萍.不同类型移动电话的电磁辐射水平.环境与健康杂志,2002,5,19(3):199
14.许宏霞。苯及同系物对女工月经情况和妊娠结局的影响.中华误诊学杂志,2002,2(2):227-228
15.董红燕,刘君卓,陈冠英,等.甲醛对豚鼠肺巨噬细胞DNA的损伤作用.环境与健康杂志,1998,15(6):253-255
1. Boue J, Bou A, Lazar P. Retrospective and prospective epidemiological studies of 1500 karyotypes spontaneous human abortion. Teratology 1975; 12:11-26
2. Edmonds DK, Lindsay KS, Miller JF, Williamson E, Wood PJ. Early embryonic mortality in women. Fertil Steril 1982;38:447-453
3. Wilcox AJ, Weinberg CR, O'Connor JF, et al. Incidence of early loss of pregnancy. N Engl J Med 1988;319:189-194
4. Ohno M, Maeda T. Matsunobu A. A cytogenetic study of spontaneous abortions with direct analysis of chorionic villi. Obstet Gynecol 1991;77:394-398
5. Jacobs PA, Hassold T. Chromosome abnormalities: origin and etiology in abortions and livebirths. In: Vogel F, Sperling K, eds. Human Genetics. Berlin: Springer-Verlag; 1987:233-244
6. Neilson J, Wohert M. Chromosome abnormalities found among 34910 newborn children: results from a 13-years incidence study in Arhus, Denmark. Hum Genet 1991 ;87:81-83
7. Stephenson MD, Awartani KA, Robinson WP. Cytogenetic analysis of miscarriage from couples with recurrent miscarriage: a case-control study. Hum Reprod 2002; 17:446-451
8. Golbus MJ: Chromosome aberrations and mammalian reproduction. In Mastroianni L, Biggers J, Sadler W(eds):Fertilization and Embryonic Development in vitro. New York, Plenum Press, 1981.
9. Sugiura-Ogasawara M, Ozaki Y, Sato T, Suzumori N, Suzumori K. Poor prognosis of recurrent aborters with either maternal or paternal reciprocal translocations. Fertil Steril 2004;81:367-373
10. Goddijn M, Joosten JH, Knegt AC, et al. Clinical relevance of diagnosis structural chromosome abnormalities in couples with repeatd miscarriage. Hum Reprod 2004; 19:1013-1017
1.Bakhtiar R,Nelson RW.Electrospray ionization and matrix-assisted laser desorption ionization mass spectrometry.Emerging technologies in biomedical sciences.Biochem Pharmacol.2000;59:891-905.
2.Szallasi Z.Bioinformatics.Gene expression patterns and cancer.Nat Biotechnol.1998;16:1292-1293.
3.Lieshout EM,Knapen MF,Lange WP,Steegers EA,Peters WH Localization of glutathione S-transferases alpha and pi in human embryonic tissues at 8 weeks gestational age.Hum Reprod.1998May;13(5):1380-6.
4.Clarson LH,Greenwood SL,Mylona P,Sibley CP.Inwardly rectifying K(+) current and differentiation of human placental cytotrophoblast cells in culture.Placenta.2001 Apr;22(4):328-36.
5.Momoyo Sonoda,Fujio Okamoto,Hiroshi Kajiya Amino Acid-Permeable Anion Channels in Early Mouse Embryos and Their Possible Effects on Cleavagel.BIOLOGY OF REPRODUCTION 2003 68,947-953
6.Jarabak J,Adams JA,Williams-Ashman HG,et el.Purification of 17beta-hydroxysteroid dehydrogenase of human placenta and studies on its transhydrogenase function.J Biol Chem,1962,237:345-357
7.Luu-The V,Dufort I,Pelletier G,et al.Type 5 17beta-hydroxysteroid dehydrogenase:its role in the formation of androgens in women.Mol Cell Endocirinol 2001,171:77-82
8.RaynalP,PollardHB.Annexin:the problem of assessing the biological role for gene family of multifunctional calcium and phospholipid-bind-ingproteins.BiochemBiophysActa,1994,1147:63-93.
9.Sun M,Liu Y,Gibb W.Distribution of annexin I and II in term human fetal membranes,deciduas and placenta.Placenta.1996 Mar-Apr;17(2-3):181-4.
10.周升,符史干,沈行良 一氧化氮合酶在心血管内皮细胞中表达的调控中国热带医学,2006;6:697-699
11.钱卫平,谭玉梅,宋丹等.1280例自然流产患者的细胞遗传学分析.中南大学学报(医学版),2005,30:258-260
12.Eber SW,Pekrun A,Bardosi A,et al.Triosephosphate isomerase deficiency:haemolytic anaemia, myopathy with altered mitochondria and mental retardation due to a new variant with accelerated enzyme catabolism and diminished specific activity. Eur J Pediatr ,1991,150:761-766
13. Smith WL, Dewitt DL Prostaglandin endoperoxideHsynthases-1 and -2. Adv Immunol 1996, 62:167-215
14. Kelly RW.Inflammatory mediators and parturition. Rev Reprod 1996, 1:89-96
15. Olofsson JI, Leung PC Prostaglandins and their receptors: implications for ovarian physiology. Biol Signals 1996 ;5:90-100
16. Lupulescu A Prostaglandins, their inhibitors and cancer. Prostaglandins Leukotrienes Essent Fatty Acids 1996 ;54:83-94
17. Vadillo-Ortega F, Beltran J, Mateo H, Monozon F Phospholipase A2 and premature membrane rupture. Ginecol Obstet Mex 1994; 62:143-145
18. Mitchell M, Bibby J, Hicks B, Turnbull A Specific production of prostaglandins E2 by human amnion in vitro. Prostaglandins 1978 15:377-382
19. Okazaki T, Casey M, Okita JR, MacDonald P, Johnston J Initiation of parturition Ⅻ. Biosynthesis and metabolism of prostaglandins in human fetal membranes and uterine deciduas. Am J Obstet Gynecol 1981; 139:373-381
20. Okita RT, Okita JR Prostaglandin-metabolizing enzymes during pregnancy: characterization of NAD1-dependent prostaglandin dehydrogenase, carbonyl reductase, and cytochrome P450-dependent prostaglandin V-hydroxylase. Crit Rev Biochem Mol Biol 1996 31:101-126
21. Ensor CM, Tai HH 15-hydroxyprostaglandin dehydrogenase. J Lipid Mediat Cell Signal 1995 12:313-319 1983
22. Krook M, Marekov L, Jo¨rnvall HPurification and structural characterization of placental NAD1-linked 15-hydroxyprostaglandin dehydrogenase. The primary structure reveals the enzyme to belong to the short-chain alcohol dehydrogenase family. Biochemistry 1990; 29:738-743
23. Erwich JJHM, Keirse MJNC Placental localization of 15-hydroxy-prostaglandin dehydrogenase in early pregnancy and term pregnancy. Placenta 1992 ; 13:223-229
24. Kelly RW Pregnancy maintenance and parturition: the role of prostaglandin in manipulating the immune and inflammatory response. Endocr Rev 1994; 15:684-706
25. Sangha RK, Walton JC, Ensor CM, Tai HH, Challis JRG Immunohistochemical localization, messenger ribonucleic acid abundance, and activity of 15-hydroxyprostaglandin dehydrogenase in placenta and fetal membranes during term and preterm labor. J Clin Endocrinol Metab 1994;78:982-989
26. Patel FA, Clifton VL, Chwalisz K, Challis JRG Steroid regulation of prostaglandin dehydrogenase activity and expression in human term placenta and chorio-decidua in relation to labor. J Clin Endocrinol Metab 1999; 84:291-299
27. Cheng L, Kelly RW, Thong KJ, Hume R, Baird DT The effects of mifepristone (RU486) on prostaglandin dehydrogenase in decidual and chorionic tissue in early pregnancy. Hum Reprod 1993; 8:705-709
28. Mckeown K. J, Challis J. R. G Regulation of 15-Hydroxy Prostaglandin Dehydrogenase by Corticotrophin-Releasing Hormone through a alcium-Dependent Pathway in Human Chorion Trophoblast. Cells, 2003; J Clin Endocrinol Metab 88: 1737-1741
29. Massa R, Marliera LN, Martorana A, etal. Intracellular localization and isoformexpression of the voltage dependendation channel(VDAC)in normal and dystrophic skeletal muscle. Muscle Res Cell Motil,2000,21(5):433 442.
30. Douglas CW. Mitochondrial diseases in man and mouse. Science, 1999,283:1482-1488.
31. Zamzami N, Hirsch T, Dallaporta B, et al. Mitochondrial implicationin accidental and programmed cell death: apoptosisan necrosis. Bioenergetics&Biomembranes, 1997,29:185-193
32. Green DR, Reed JC. Mitochondria and apoptosis. Science 1998,281(5318): 1309 1312.
33. Susin SS, Earnshaw WC. Apoptosis: Acellular poison cupboard . Nature, 1999;397:387 389.
34. Liu X, Kim CN, Yang J, etal. Induction of apoptotic program in cell free extracts: requirement fo dATP and cytochromec. Cell, 1996; 86 :147- 157.
35. Gross A, McDnnell JM, Korsmeyer SJ. Bcl 2 family members an Themitochondria in apoptosis. Genes&Development, 1999; 13:1899- 1911.
36. Shimizu S, Narita M, Tsujimoto Y. Bcl 2 family proteins regulat the release of apoptogenic cytochrome C by themitochondria channel VDAC. Nature, 1999, 399:483-487.
37. Afonso S, Romagnanol L, Babiarz B. Expression of cathepsin proteinase by mouse trophoblaetin in vivo and in vitro.J Dev Dyn 1999,216:374-84
38.王安明 陈士岭 邢福祺等。组织蛋白酶B和L在早期妊娠绒毛及蜕膜中的表达.第一军医大学学报,2005;25:1365-1368
39.杨帆,刘卫平.核糖体蛋白基因及其与人类疾病的研究进展.临床与实验病理学杂志J Clin Exp Pathol 2005 Jun;20(3):354-356
1.Sweeney AM,Meyer MR,Aarons JH,Mills JL,LaPorte RE:Evaluation of methods for the prospective identification of early fetal losses in environmental epidemiology studies.Am J Epidemiol 127:843,1988
2.Edmonds DK,Lindsay KS,Miller JF,Williamson E,Wood PJ.Early embryonic mortality in women.Fertil Steril 1982;38:447-453
3.Alberman E:The epidemiology of repeated abortion.In Beard RW,Sharp F(eds):Early Pregnancy Loss:Mechanisms and Treatment.London,RCOG;1988,P9
4.Leridon H:Human Fertility:The basic Components.Chicago,University of Chicago Press,1977
5.Boue J,Bou A,Lazar R Retrospective and prospective epidemiological studies of 1500 karyotyped spontaneous human abortion.Teratology 1975;12:11-26
6.Wilcox AJ,Weinberg CR,O'Connor JF,et al.Incidence of early loss of pregnancy.N Engl J Med 1988;319:189-194
7.Ohno M,Maeda T.Matsunobu A.A cytogenetic study of spontaneous abortions with direct analysis of chorionic villi.Obstet Gynecol 1991;77:394-398
8.Jacobs PA,Hassold T.Chromosome abnormalities:origin and etiology in abortions and livebirths.In:Vogel F,Sperling K,eds.Human Genetics.Berlin:Springer-Verlag;1987:233-244
9.Simpson JL.Incidence and timing of pregnancy losses:relevance to evaluating safety of early prenatal diagnosis.Am J Med Genet 1990;35:165-173
10. Neilson J, Wohert M. Chromosome abnormalities found among 34910 newborn children: results from a 13-years incidence study in Arhus, Denmark. Hum Genet 1991;87:81-83
11. Hassold T, Chiu D. Maternal age-specific rates of numerical chromosome abnormalities with specific reference to trisomy. Hum Genet 1985;70:11-17
12. Jacobs PA, Hassold TJ. The origin of numerical chromosome abnormalities. Adv Genet 1995;33:101-133
13. Martin RH, Ko E,Rademaker A. Distribution of aneuploidy in human gametes: comparison between human sperm and oocytes. Am J Med Genet 1991;39:321-331
14. Rubio C, Gil-Salom M, Simon C, et al. Incidence of sperm chromosome abnormalities in a risk population: relationship with sperm quality and ICSI outcome. Hum Reprod 2001; 16:2084-2092
15. Stephenson MD, Awartani KA, Robinson WP. Cytogenetic analysis of miscarriage from couples with recurrent miscarriage: a case-control study. Hum Reprod 2002; 17:446-451
16. Frequency of factors associated with habitual abortion in 197 couples. Fertil Steril 1996; 66: 24—29
17. Sugiura-Ogasawara M, Ozaki Y, Sato T, Suzumori N, Suzumori K. Poor prognosis of recurrent aborters with either maternal or paternal reciprocal translocations. Fertil Steril 2004;81:367-373
18. Goddijn M, Joosten JH, Knegt AC, et al. Clinical relevance of diagnosis structural chromosome abnormalities in couples with repeated miscarriage. Hum Reprod 2004; 19:1013-1017
19. Stephenson MD, Sierra S. Reproductive outcomes in recurrent pregnancy loss associated with a potential carrier of a structural chromosome rearrangement. Fertil Steril 2006;
20. Carp H, Feldman B, Oelsner G, Schiff E. Parental karyotype and subsequent live births in recurrent miscarriage. Fertil Steril 2004;81:1296-1301
21. Bell KA, Van Deerlin PG, Haddad BR, Feinberg RF. Cytogenetic diagnosis of " normal 46,XX" Karyotypes in spontaneous abortions frequently may be misleading. Fertil Steril 1999;71:334-341
22. Lomax B, Tang S, Separovic E, et al. Comparative genomic hybridization in combination with flow cytometry improves results of cytogenetic analysis of spontaneous abortions.Am J Hum Genet. 2000;66(5):1516-21.
23. Philipp T, Feichtinger W, Van Allen MI, et al. Abnormal embryonic development diagnosed embryoscopically in early intrauterine deaths after in vitro fertilization: a preliminary report of 23 cases. Fertil Steril 2004;82:1337-1342
24.Ferro J,Martinez MC,Lara C,et al.Improved accuracy of hysteroembryoscopic biopsies for karyotyping early missed abortions.Fertil Steril 2003;80:1260-1264
25.Ober C,Aldrich CL,Chervoneva I,et al.Variation in the HLA-G promoter region influences miscarriage rates.Am J Hum Genet 2003;72:1425-1435
26.Karhukorpi J,Laitinen T,Tiilikainen AS.HLA-G polymorphism in Finnish couples with recurrent spontaneous miscarriage.Br J Obstet Gynecol 1997;104:1212-1214
27.Penzea M,Rajcy K,Gyodi E,et al.HLA-G gene polymorphism in the normal population and in recurrent spontaneous abortion in Hungary.Transplant proc 1999;31:1832-1833
28.Pfeiffer KA,Fimmers R,Engels G,et al.The HLA-G genotype is potentially associated with idiopathic recurrent spontaneous abortion.Mol Hum Reprod 2001;7:373-378
29.Aldrich CL,Stephenson MD,Karrison T,et al.HLA-G genotype and pregnancy outcome in couples with unexplained recurrent miscarriage.Hum Reprod 2001;7:1167-1172
30.Edwarda RG,Gardner RL.Choosing sex before birth.New Scientist 1968;38:218-220
31.Harper JC,Coonen E,RAmaekers FC,et al.Identification of the sex of human preimplantation embryos in two hours using an improved spreading method and fluorescent in-situ hybridization(FISH) using directly labeiied probes.Hum Reprod 1994;9:721-724
32.Munne S,Magli C,Cohen J,et al.Positive outcome after preimplantation diagnosis of aneuploidy in human embryos.Hum Reprod 1999;14:2191-2199
33.Vidal F,Gimenez C,Rubio C,et al.FISH preimplantation diagnosis of chromosome aneuploidy in recurrent pregnancy wastage.J Assist Reprod Genet 1998;15:310-313
34.Pellicer A,Rubio C,Vidal F,et al.In vitro fertilization plus preimplantation genetic diagnosis in patients with recurrent miscarriage:an analysis of chromosome abnormalities in human preimplantation embryo.Fertil Steril 1999;71:1033-1039
35.Golbus MJ:Chromosome aberrations and mammalian reproduction.In Mastroianni L,Biggers J,Sadler W(eds):Fertilization and Embryonic Development in vitro.New York,Plenum Press,1981.
36.Rocklin RE,Kitzmiller JL,Carpenter CB,et al:Maternal fetal relation.N Engl Med 295:1209,1976
37.杨珏琴等 原因不明复发性流产HLA相关性的初步研究。中国免疫学杂志,1999;15(3):135-137
38.居中亮,范丽安,陆丽华等 T辅助细胞1、2细胞因子平衡与正常妊娠及复发性流产关系的初步探讨。中华妇产科。 2000; 5 (8): 473-475.
39. Mowbray JF, Liddell H, Underwood JL,et al: Controlled trial of treatment of recurrent spontaneous abortion by immunization with paternal cells. Lancet 1:942,1985.;
40. Ito K, Obata F, Tanaka T et al., Analysis of HLA-DR types of unexplained recurrent spontaneous aborters in the Japanes population by oligonucleotide DNA typing. Tissue Antigens, 1992;40:204
41. Cauchi MN, Lim D, Young DE, et al: Treatment of recurrent aborters by immunization with paternal cells-controlled immunol 25:16,1991
42. Strassman EO:Fertili and unification of double uterus. Fertil Steril 17:165,1966
43. March CM, Isarel R: Hysteroscopic management of recurrent abortions caused by septate uterus. Am J Obste Gynecol 156:834,1987
44. Jones WS:Obsteric significance of female genital anomalies. Obstet Gynecol 10:113,1957
45. Capraro VJ, Gallego MB:Vaginal agenesis. Am J Obste Gynecol 124;98,1976
46. Cowchock S, Dehoratius RD, Wapner RJ, et al: Subclinical autoimmune disease and unexplained abortion. Am J Obste Gynecol 150:367,1984
47. Harger JH,Rabin BS, Marchese SG: The prognostic value of antinuclear antibigies in women with recurrent pregnancy losses: A prospective controlled study. Obste Gynecol 73:419,1989
48. Lubbe WF, Butler WS,palmer SJ, et al:Lupus anticoagulant in pregnancy. Br J Obste Gynaecol 91:357,1984;
49. Unander Am,Norberg R, Hahn L,et al: anticardiolipin antibodies and complement an ninety-nine women with habitual abortion. Am J Obste Gynecol 156:114,1987
50. Pedowitz P, Shelvin EL:Perinatal mortality in the unsuspected diabetic. Obste Gynaeco 9:524,1957.
51. Kalter H:Diabetes and spontaneous abortion:A historical review. Am J Obste Gynecol 156:1243,1987
52. Tupper C,Weil RJ: The problem of spontaneous abortion IX. The treatment of habital aborters by psychotherapy. Am J Obste Gynecol 83:421,1962
53. James WH: The problem of spontaneous abortion X.The efficacy of psychotherapy. Am J Obste Gynecol 85:38,1963a
54. Stray-Pedersen B, Stray- Pedersen S: Etiologic factors and subsequent reproductive performance in 195 couples with a prior history of nabitual abortion.Am J Obste Gynecol 148:140,1984
55.Kline J,Stein Z,Susser M et al:Environmental influences on early reproductive loss in a current New York City study.In Porter IH,Hook EB(eds):Human Embryonic and Fetal Death.New York,Academic Press,1980.
56.Ecker J,Laufer M,Hill JA:Measurement of embryotoxic factors is predictive of pregnancy outcome in women with a history of recurrent abortions.The Pacific Coast Fertility Soiety 40th Annual Meeting,Indian Wells.California,April 8-12,1992,Abst 0-011
57.Grimaldi S,Pasquali E,Barbatano L,et al.Exposure to a 50 Hz Electromagnetic field induces activation of the Epstein-Barr virus genome in latently infected human lymphoid cells.J Environ Pathol Toxicol Oncol,1997,16:205-207
58.张彦文。微波辐射与细胞凋亡。国外医学卫生学分册。1999,26:9-14
59.Spica V,Mucci N,Ursini,et al.Etsl oncogene induction by ELF modulated 50 MHZ rediafrequency electromagnetic field.Bioelectromagnetics,2000,21:8-18
60.黄相刚,曹兆进。电磁辐射对基因的影响。卫生毒理学杂志,2002,16(3):188-191
61.马毓,刘兰女,杨青霞,等。电磁辐射对人体染色体结构稳定的影响。中国优生与遗传杂志,2002,10(5):18
62.Smith EM,Hammonds Ehlers M,Clark MK,et al.Occupational exposures and risk of female infertility.J Occup Environ Med,1997,39(2):138
63.王水明,王德文。电磁辐射对妊娠及子代的影响。解放军预防医学杂志,2002,20(5):385-387
64.孟丽,彭瑞云。电磁辐射对内分泌的影响。中华物理医学与康复杂志,2004,26(4):251-254
65.Marcus M,McChesney R,Golden A,et al.Video display terminals and miscarriage.J Am Med Women Assoc,2000,55(2):84
66.Spica V,Mucci N,Ursini,et al.Etsl oncogene induction by ELF modulated 50 MHZ rediafrequency electromagnetic field.Bioelectromagnetics,2000,21:8-18
67.朱大明,年冀,何志辉,等。电磁辐射环境的潜在致突变水平。环境监测管理与技术,2005,17(1):19-21
68.Singh N,Rudra N,Bansal P,et al.Poly ADP ribosylation as a possible mechanism of microwave-biointeraction.Indian J Physical Pharmacol,1994,38:181-184
69.许宏霞。苯及同系物对女工月经情况和妊娠结局的影响。中华误诊学杂志,2002,2(2):227-228
70.吴奇,刘俊茹,郝丽萍。不同类型移动电话的电磁辐射水平。环境与健康杂志,2002,5,19(3):199
71.董红燕,刘君卓,陈冠英,等。甲醛对豚鼠肺巨噬细胞DNA的损伤作用。环境与健康杂志,1998,15(6):253-255