The polymorphic hMSH5 C85T allele augments radiotherapy‐induced spermatogenic impairment
The polymorphic hMSH5 C85T allele augments radiotherapy‐induced spermatogenic impairment
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DOI：
10.1111/andr.12203
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发表时间：
2016-07
期刊：
影响因子：
4.5
通讯作者：
Y. Zhu;G. Gao;L. Xia;X. Li;X. Wu;C. Her;K. Xu
中科院分区：
文献类型：
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作者：
Y. Zhu;G. Gao;L. Xia;X. Li;X. Wu;C. Her;K. Xu
hMSH5 C85T多态性（编码hMSH5 P29S）与男性不育和辐射诱导的凋亡反应相关。然而，迄今为止，hMSH5 C85T多态性与放射治疗的癌症患者精子中DNA损伤积累的潜在关联在很大程度上是未知的。我们调查了113例睾丸生殖细胞肿瘤（TGCT）患者放疗前后hMSH5 C85T等位基因和基因型频率、精液常规分析和精子DNA片段化指数（DFI）。hMSH5C85T等位基因与TGCT的发生无关。然而，与CC基因型相比，CT + TT基因型的TGCT患者在放疗后表现出显著的精子计数、精子形态和DFI改变。最后，DSB修复测定的结果表明，hMSH5 P29 S可以通过释放易错的非同源末端连接来增强放射治疗诱导的DNA损伤。总之，我们的研究表明，hMSH5 C85T变异可能通过损害辐射诱导的DNA损伤的修复而影响放射治疗引起的长期副作用的严重程度。
The hMSH5 C85T polymorphism (encoding hMSH5 P29S) is associated with male infertility and radiation‐induced apoptotic response. To date, however, the potential association of hMSH5 C85T polymorphism with DNA damage accumulation in spermatozoa of cancer patients treated with radiotherapy is largely unknown. We investigated hMSH5 C85T allele and genotype frequencies, routine semen analysis and sperm DNA Fragmentation Index (DFI) in 113 testicular germ cell tumor (TGCT) patients before and after radiotherapy. The hMSH5 C85T allele is not associated with the occurrence of TGCT. However, in comparison with the CC genotype, TGCT patients with the CT + TT genotypes showed significantly altered sperm counts, sperm morphology and DFI after radiotherapy. Finally, the results of the DSB repair assay demonstrated that hMSH5 P29S could enhance radiotherapy‐induced DNA damage by unleashing error‐prone non‐homologous end joining. Together, our studies indicate that the hMSH5 C85T variation could have an impact on the severity of radiotherapy‐provoked long‐term side effects through compromising the repair of radiation‐induced DNA lesions.