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【摘要】 无精少弱精子症是引起男性不育的主要原因,其主要的病因是生精障碍,对生精障碍的病因学研究、从基因水平了解和治疗是目前研究的主要问题,现就这几方面的研究进展情况作一综述。
【关键词】 无精症;少弱精症;生精障碍;基因;不孕不育
目前全世界不育夫妇约占已婚夫妇的15%,其中由男方原因引起的不育占50%[1],男性不育的精液检查主要表现为无精子症及少弱精子症。少精子症是指禁欲2～7 d一份精液电脑分析中精子密度10×109/L;中度少精子症:精子密度5×109/L;重度少精子症:精子密度30%或A级10%;中度弱精子症:A级+B级精子30%,其中A级精子 3 无精及少弱精子症与生精障碍的临床病因学研究
3.1 性激素相关基因 一般认为雄激素受体(AR)基因的突变是导致不育的主要原因。AR基因第一外显子存在CAG三核苷酸重复序列,有人认为重复序列的程度与不育存在一定的关系。但目前仍存在争议[18]。其他性激素相关基因包括:(1)卵泡刺激素受体(FSHR)基因;(2)黄体生成素受体(LHR)基因;(3)促性腺激素基因;(4)促性腺激素释放激素受体(GnRHR)基因。
3.2 先天性输精管缺如(Congenital absence of the vasdeferens,CAVD)CAVD是梗阻性无精子症和男性不育的重要原因。临床多见先天性双侧输精管缺如(CBAVD)和先天性单侧输精管缺如(CUAVD)、节段性缺如。目前认为CAVD大部分与囊性纤维化跨膜转运调节物(CFTR)基因突变和中肾管发育缺陷有关[19, 20]。CBAVD均为无精子症,通常精液量少,pH值低。CUAVD和节段性缺如精液可表现为少精子症、弱精子症或梗阻性无精子症,精液量可正常。精浆果糖可表现为无、减少或正常。
3.3 抗精子抗体(AsAb)男性不育者中AsAb的发病率在6%～l1%。是男性不育的常见原因。造成生育功能损害的机制包括降低精子活力、存活率、宫颈黏液穿透力及损害精子卵子结合。产生AsAb的原因包括:(1)梗阻因素;(2)睾丸钝伤;(3)睾丸活检;(4)睾丸炎;(5)生殖道感染。Madar等发现,AsAb在弱精子症患者中较为常见,但是在正常生育男性中也有发现。故对其病理生理机制仍需进一步探讨[21]。
3.4 微量元素缺乏锌是生殖系统内重要的微量元素,锌缺乏可造成一系列不良的影响,主要包括:影响青春期男性生殖器官和第二性征的发育,影响精子的活动能力,削弱机体的免疫功能而容易患前列腺炎、附睾炎等感染性疾病,影响促性腺激素的分泌,还可以抑制机体对有害金属铅的排泄。弱精子症、少弱精子症患者精子的发生及运动功能下降可能与精浆锌含量的低下呈正相关[22]。所以,适当补充锌可以维持并改善生育功能。
3.5 其他不良生活习惯和生活方式包括一些影响生育的食物,如粗制棉籽油里的棉酚、食品添加剂、着色剂、防腐剂、含有雌激素及其类似物的食品等。最新的研究表明,吸烟和精液量、精子总数、精子活力有着明显的相关关系,吸烟剂量和T、HL、HL/fT之间成正比关系[23]。
4 展望
目前,越来越多对无精症和少弱经症病因的研究报道表明,很有可能是遗传因素导致了一些男性的生育力低下。但是把有效而精确的基因整合转移到靶组织的基因组时,还存在着相当大的问题。找到无精症和少精症患者病因,从基因的水平来治疗男性不育是有效的方法。但目前存在的主要障碍是:对特异性的基因缺陷缺乏清晰的认识;基因损伤导致男性不育的实质还不十分清楚。随着基因芯片技术的发展,运用基因芯片能够对精子发生所涉及的普通基因和睾丸特异基因进行大规模筛选,能够显示一系列与生殖相关基因缺陷,从分子水平上全面了解和治疗无精症或少弱精症的生精障碍病因及其机理目前仍需进一步探究。
参 考 文 献
[1] Dada R, Gupta NP,Kucheria K.Molecular screening for Yq microdeletion in men with idiopathic oligozoospermia and azoospermia.J Biosci,2003, 28(2):163-168.
[2] Hopps CV, M ielnik M, Goldstein M,et al. Detection of sperm in men with Y chromosome microdeletions of the AZFa,AZFb,and AZF cregions.Hum Reprod,2003,18(8):1660-1665.
[3] Tiepolo L,Zufardi O. Localization of factors controlling spermatogenesis in the nonfluorescent portion of the human Y chromosome long arm.Hum Genet,1976,34(2):119-124.
[4] Sun C, Skaletsky H, Birren B,et al. An azoospermic man with a denovo point mutation in the Y-chromosomal gene USP9Y.NatGenet,1999,23:429-432.
[5] Foresta C, Ferlin A.Moro E1Deletion and expression analysis of AZFa genes on the human Y chromosome revealed a major role of DBY in male infertility.Hum Mol Genet,2000,9:1161-1169.
[6] Pao-Lin K, Ying-Hung L, Yen-Ni T,et al. Transcriptional levels of four Y chromosome linked AZF genes in azoospermic men and their association with successful sperm retrieval.Urology,2004,63:131-163.
[7] Chai NN,Salido EC.Yen PH1Multiple functional copies of the RBM gene family,a spermatogenesis candidate of the human Y chromosome.Genetics, 1997,45:355-361.
[8] Kuroda-Kawaguchi T, Skaletsky H, Browm L G,et al. The AZF region of the Y chromosome features massive palindromes and uniform recurrent deletion in infertile men.Nat Genet,2001,29:279-286.
[9] Reijo R, Alagappan RK, Patrizio P,et al. Severe oligospermia resulting from deletions of the Azoospermia Factor gene on the Y chromosome.Lancet, 1996,347:1290-1293.
[10] Reijo RA, Dorfman DM, Slee R,et al.DAZ family proteins exist Through out male cell development and transit from nucleus to cytoplasm at meiosis in humans and mice.Biol Reprod,2000,63:1490-1496.
[11] Kuo PL,Lin YH, Teng YN,et al.Transcriptional levels of four Y chromosome linked AZF genes in azoospermic men and their association with successful sperm retrieval.Urology,2004,63:131-136.
[12] Sawai H, Komori S,Koyama K1Molecular analysis of the Y chromosome AZFc region in Japanese infertile males with spermato genic defects.J Reprod Immun,2002,53:37-44.
[13] Kent-First M,Muallem A,Shultz J,et al.Defining regions of the Y chromosome responsible for male infertility and identification of a fourth AZF region(AZFd) by chromosome microdeletion detection.J Mol Reprod Dev,1999,53(1):27-41.
[14] Seboun E, Barbaux S,Bourgeron T,et al. Gene sequence, locolization,and evolutionary conservation of DAZLA,a candidate male sterility gene. Genomics,1997,41:227-235.
[15] Miyamoto T, Hasuike S, Yogev L,et al.Azoospermia in patients heterozygous for a mutation in SYCP3.Lancet,2003,362:1714-1719.
[16] Yuan L, Liu J G, Hoja MR,et al. Female germ cell aneuploidy and embryo death in mice lacking the meiosis-specific protein SYCP3. Science,2002, 296:1115-1118.
[17] Miyamoto T, Hasuike S, Yogev L,et al.Azoospermia in patients heterozygous for a mutation in SYCP3.Lancet,2003,362:1714-1719.
[18] Rajpert-De Meyts E, Leffers H, Petersen JH,et al. CAG repeat length in androgen-receptor gene and reproductive variables in fertile and infertile men.Lancet,2002,359(9300):44-46.
[19] Chillon M, Casals T, Mereier B, et al. Mutations in the cystic fibrosis gene in patients with congenital absence of the vas deferens.N Engl J Med,1995,332(22):1475-1480.
[20] Schlegel PN, Shin D, Goldstein M. Urogenital anomalies in men with congenital absence of the vas deferens.J Urol,1996,155(5):1644-1648.
[21] Madar J, Urbanek V, Chaloupkova A,et al. Role of sperm antibodies and cellular autoimmunity to spermin the pathogenesis ofmale infertility .Ceska Gynekol,2002,67(1):3-7.
[22] Zhao RP, Xiong CL. Zinc content analysis in serum, seminal plasma and spermatozoa of asthenozoospermic and oligoasthenozoospermic patients.Zhonghua Nan Ke Xue,2005,11(9):680-682.
[23] Ramlau-Hansen CH, Thulstrup AM, Aggerholm AS, et al. Is smoking a risk factor for decreased semen quality? A cross sectional analysis.Hum Reprod,2007,22(1):188-196.
