Polymorphisms of nucleotide-excision repair genes may contribute to sperm DNA fragmentation and male infertility

REPRODUCTIVE BIOMEDICINE ONLINE

卷:21

Article

Gu, Aihua¹  Ji, Guixiang¹  Zhou, Yong²  Long, Yan¹  Shi, Xiangguo¹  Fu, Guangbo³  Wang, Shoulin¹  Song, Ling¹  Wang, Xinru¹ 

[1] Nanjing Med Univ, Key Lab Reprod Med, Inst Toxicol, Nanjing 210029, Peoples R China

[2] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA

[3] Nanjing Med Univ, Huai An Affiliated Hosp 1, Dept Urol, Huaian, Peoples R China

关键词: male infertility;    nucleotide-excision repair (NER);    polymorphisms;    sperm DNA damage;    xeroderma pigmentosum group A gene (XPA);   

DOI  :  10.1016/j.rbmo.2010.06.025

来源: Elsevier

【 摘 要 】

The nucleotide-excision repair (NER) system is crucial for the removal of bulky DNA adducts during spermatogenesis. Dysfunction of its repair capacity is likely related to the increased susceptibility to DNA damage. In this study, four polymorphisms in NER pathway (XPA(-4) G/A, ERCC1 C8092A, XPD Lys751Gln and XPF Ser835Ser) were selected to evaluate their potential impact on sperm DNA damage and male infertility. Genotypes were determined by PCR-restriction fragment length polymorphism. Sperm DNA damage was evaluated by TdT-mediated dUDP nick-end labelling assay. A case-only study of 620 infertile men found a significant association between XPA(-4) G/A polymorphism and sperm DNA damage. Individuals with the XPA(-4) A allele showed more sperm DNA damage and lower sperm concentration than G allele carriers. Further analysis, including 620 patients and 385 controls, revealed a 1.52-fold risk (95% CI 1.08-2.02) of developing male infertility in the XPA(-4) AA carriers compared with noncarriers. Luciferase assay verified that the promoter with the XPA(-4) A allele had a lower transcriptional activity than that with the G allele. These data provide the first evidence that 4 G/A polymorphism in XPA promoter alters its transcriptional activity and, thus, might contribute to sperm DNA damage and male infertility. Online (C) 2010, Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

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