Joint effects of XRCC1 polymorphisms and polycyclic aromatic hydrocarbons exposure on sperm DNA damage and male infertility.
X-ray repair cross-complementing group 1 (XRCC1) plays a role in repairing polycyclic aromatic hydrocarbons (PAHs)-induced DNA damage. We examined the effects of exposure to PAHs and XRCC1 polymorphism, alone or combined, on sperm DNA integrity and male fertility. A total of 620 idiopathic infertile subjects and 273 fertile controls were recruited in this study. PAHs exposure was indicated by urinary 1-hydroxypyrene level. Genotypes were determined by PCR-RFLP, and sperm DNA damage was detected by Tdt-mediated dUTP nick end labelling assay using flow cytometry. A positive correlation was found between PAHs exposure and sperm DNA damage (beta coefficients = 0.183, p < 0.001), whereas there was no significant association between the XRCC1 polymorphisms and sperm DNA damage. However, when the patients were dichotomized for PAHs exposure, higher sperm DNA damage was found among 399Gln allele carriers compared with the wild-type homozygotes (p = 0.033). Further analysis based on a case-control study revealed the joint effect of XRCC1-399 polymorphism and PAHs exposure on the risk of male infertility (p interaction = 0.041). These findings provided the first evidence about potential joint effects of PAHs exposure and DNA repair gene polymorphisms on male reproductive system and may be helpful in improving our understanding of the etiology of male infertility.
Ji
Guixiang
G
Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing, China.
Gu
Aihua
A
Zhu
Pengfei
P
Xia
Yankai
Y
Zhou
Yong
Y
Hu
Fan
F
Song
Ling
L
Wang
Shoulin
S
Wang
Xinru
X
D000328:Adult; D016022:Case-Control Studies; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000235:genetics*; D006801:Humans; D020287:In Situ Nick-End Labeling; D007248:Infertility, Male / Q000139:chemically induced* / Q000235:genetics*; D008297:Male; D011083:Polycyclic Compounds / Q000633:toxicity* / Q000652:urine; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D013094:Spermatozoa / Q000187:drug effects*; D000076105:X-ray Repair Cross Complementing Protein 1
D004268:DNA-Binding Proteins; D011083:Polycyclic Compounds; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human