DNA mismatch repair and infertility.
DNA mismatch repair and infertility.
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DOI：
10.1097/mou.0b013e32833f1c21
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发表时间：
2010-11
影响因子：
2.5
通讯作者：
Lamb DJ
中科院分区：
文献类型：
--
作者：
Mukherjee S;Ridgeway AD;Lamb DJ
探讨DNA修复机制异常在男性不育中的意义。在小鼠模型中，DNA修复缺陷导致多种精子发生缺陷。越来越多的证据表明DNA修复缺陷在人类非梗阻性无精子症中的重要性。表观遗传学变化也可能在不孕症中发挥关键作用。细胞中的DNA需要不断修复，以确保DNA复制的保真度，保持基因组的稳定性，并确保物种的繁殖。DNA修复和重组机制在物种中高度保守，这些途径的失活可能导致复制和重组错误。本文综述了DNA损伤的类型和DNA修复途径，特别是高度保守的减数分裂调节因子DNA错配修复蛋白。这些蛋白质中的一些的靶向缺失导致不育并且在突变小鼠模型中易患肿瘤。有证据表明，在人类男性不育症中，这些蛋白质中的一些丢失。由于有缺陷的DNA修复与突变表型有关，因此需要进一步评估这些使用辅助生殖技术受孕的不育男性的后代传播风险。
To highlight the significance of the abnormal DNA repair mechanism in male infertility. DNA repair defects cause a variety of spermatogenic defects in mouse models. Evidence is accumulating to demonstrate the importance of DNA repair defects in human non-obstructive azoospermia. Epigenetic changes may also play a crucial role in infertility. The DNA in the cell needs to be constantly repaired to ensure fidelity of DNA replication, to maintain genome stability and to ensure propagation of species. The DNA repair and recombination machineries are highly conserved across the species and inactivation of these pathways may lead to replication and recombination errors. This review summarizes types of DNA lesions and DNA repair pathways, particularly focusing on highly conserved meiotic regulators the DNA mismatch repair proteins. Targeted deletions of some of these proteins results in infertility and predisposes to tumor in mutant mouse models. There is evidence for loss of some of these proteins in human male infertility. Because defective DNA repair is associated with a mutator phenotype, the risk of transmission to the offspring of these otherwise infertile men conceived using an assisted reproductive technology needs further evaluation.