Defective recombination in infertile men
Defective recombination in infertile men
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DOI：
10.1093/hmg/ddh302
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发表时间：
2004-11-15
影响因子：
3.5
通讯作者：
Pera, RAR
中科院分区：
文献类型：
--
作者：
Gonsalves, J;Sun, F;Pera, RAR
2%的男性由于精子生产缺陷而不育。在10-15%的病例中，检测到包含关键精子发生基因的Y染色体缺失;在其余病例中，不孕症的原因尚不清楚。在模式生物中，重组基因的缺陷会导致不育、生殖细胞非整倍性以及随后发育出不能存活或异常的后代。一些研究也将不育与男性和女性生殖细胞非整倍体的高发生率联系起来。因此，我们推断，有缺陷的重组可能是男性不育的主要原因与穷人或没有精子生产，我们进行了第一次比较的重组参数的人口内的单个精母细胞不育和生育的男性谁报告辅助生殖。我们观察到10%的非梗阻性无精子症男性的重组频率明显低于精子发生正常的男性。此外，当我们只对那些由于精子发育过程中的停滞而被病理诊断为“成熟停滞”的男性进行分析时，大约一半的人在重组中有可检测到的缺陷。相比之下，没有一个精子发生正常的男性有重组缺陷。因此，这项研究提供了直接的证据表明，重组缺陷与相当比例的不育男性精子生产不良有关。这一观察结果对辅助生殖技术的使用的影响尤其值得考虑，因为在减数分裂期间需要重组来引入遗传变异并确保正确的染色体分离。
Two percent of men are infertile owing to defects in sperm production. In 10-15% of cases, Y chromosome deletions that encompass critical spermatogenesis genes are detected; in the remaining cases, the cause of infertility is unknown. In model organisms, defects in recombination genes cause infertility, germ cell aneuploidy and subsequent development of inviable or abnormal progeny. Several studies have also linked infertility and higher rates of germ cell aneuploidy in men and women. Thus, we reasoned that defective recombination may be a major cause of infertility in men with poor or no sperm production and we performed the first comparison of recombination parameters within populations of single spermatocytes from infertile and fertile men who reported for assisted reproduction. We observed that 10% of non-obstructive azoospermic men had significantly lower recombination frequencies than men with normal spermatogenesis. Furthermore, when we focused our analysis only on those men who had a pathological diagnosis of 'maturation arrest' due to arrest during sperm development, about half had detectable defects in recombination. In contrast, none of the men with normal spermatogenesis had defects in recombination. Thus, this study provides direct evidence that defects in recombination are linked to poor sperm production in a significant percentage of infertile men. Implications of this observation for the use of assisted reproductive technologies are especially relevant to consider, given that recombination is required to both introduce genetic variation and insure proper chromosome separation during meiosis.