Abnormal meiotic recombination in infertile men and its association with sperm aneuploidy
Abnormal meiotic recombination in infertile men and its association with sperm aneuploidy
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DOI：
10.1093/hmg/ddm246
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发表时间：
2007-12-01
影响因子：
3.5
通讯作者：
Ma, Sai
中科院分区：
文献类型：
--
作者：
Ferguson, Kyle A.;Wong, Edgar Chan;Ma, Sai
早期减数分裂事件的缺陷被认为在男性不育中起关键作用;然而，关于早期减数分裂事件与人类精子染色体构成之间的关系知之甚少。因此，我们分析了睾丸组织从26名男子（9生育和17不育的男子），使用免疫荧光技术检查减数分裂染色体，荧光原位杂交评估精子非整倍体。基于相对较小的样本量，我们观察到42%（5/12）的精子发生受损的男性与生育男性相比，表现出减少的全基因组重组。单个染色体的分析显示染色体特异性重组缺陷：染色体13和18二价体，只有一个单一的交叉和染色体21二价体缺乏交叉不育男性中更频繁。我们确定了两名不育男性，他们表现出一种新的减数分裂缺陷，其中性染色体未能重组：一名男性睾丸中没有精子，而另一名男性精子中的性染色体非整倍体增加，导致卵胞浆内单精子注射后发生45，X流产。当所有男性被合并时，我们观察到性染色体重组频率与精子中XY二体性之间呈负相关。性染色体之间的重叠可能是识别男性产生染色体异常精子风险的有用指标。了解导致不育男性精子非整倍体的分子机制有助于对接受辅助生殖的夫妇进行风险评估。
Defects in early meiotic events are thought to play a critical role in male infertility; however, little is known regarding the relationship between early meiotic events and the chromosomal constitution of human sperm. Thus, we analyzed testicular tissue from 26 men (9 fertile and 17 infertile men), using immunofluorescent techniques to examine meiotic chromosomes, and fluorescent in situ hybridization to assess sperm aneuploidy. Based on a relatively small sample size, we observed that 42% (5/12) of men with impaired spermatogenesis displayed reduced genome-wide recombination when compared to the fertile men. Analysis of individual chromosomes showed chromosome-specific defects in recombination: chromosome 13 and 18 bivalents with only a single crossover and chromosome 21 bivalents lacking a crossover were more frequent among the infertile men. We identified two infertile men who displayed a novel meiotic defect in which the sex chromosomes failed to recombine: one man had an absence of sperm in the testes, while the other displayed increased sex chromosome aneuploidy in the sperm, resulting in a 45, X abortus after intracytoplasmic sperm injection. When all men were pooled, we observed an inverse correlation between the frequency of sex chromosome recombination and XY disomy in the sperm. Recombination between the sex chromosomes may be a useful indicator for identifying men at risk of producing chromosomally abnormal sperm. An understanding of the molecular mechanisms that contribute to sperm aneuploidy in infertile men could aid in risk assessment for couples undergoing assisted reproduction.