Nucleotide excision repair polymorphisms, polycyclic aromatic hydrocarbon exposure, and their effects on sperm deoxyribonucleic acid damage and male factor infertility.
OBJECTIVE
To evaluate the effects of polycyclic aromatic hydrocarbon (PAH) exposure and four functional genetic polymorphisms in the nucleotide excision repair pathway, alone or combined, on sperm DNA integrity and male fertility.


METHODS
Retrospective case-only and case-control study.


METHODS
One university and three centers of clinical reproductive medicine in the Jiangsu Province of China.


METHODS
Six hundred twenty infertile men and 273 controls were recruited for the study.


METHODS
None.


METHODS
Exposure to PAHs was detected as urinary 1-hydroxypyrene level. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism, and sperm DNA damage was detected by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling assay with use of flow cytometry.


RESULTS
Increased sperm DNA damage was found to be associated significantly with increased urinary concentrations of 1-hydroxypyrene. We also observed that the xeroderma pigmentosum group A (XPA)-4 G/A polymorphism was associated with sperm DNA damage. Subjects homozygous for XPA-4 AA had significantly more sperm DNA damage compared with subjects for XPA-4 GG. Moreover, on the basis of a case-control study, a significant interaction was found between XPA-4 G/A polymorphism and PAH exposures on the sperm DNA damage risk (odds ratio = 2.86, 95% confidence interval = 1.77-4.61).


CONCLUSIONS
We provide the first evidence for potential gene-environment interactions between nucleotide excision repair polymorphisms and PAH exposure on the sperm DNA damage and male factor infertility in men with no occupational exposure to PAHs.
Gu
Aihua
A
Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing, People's Republic of China.
Ji
Guixiang
G
Zhu
Pengfei
P
Zhou
Yong
Y
Fu
Guangbo
G
Xia
Yankai
Y
Song
Ling
L
Wang
Shoulin
S
Wang
Xinru
X
D000328:Adult; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D018736:DNA Adducts / Q000032:analysis / Q000652:urine; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000187:drug effects / Q000235:genetics; D006801:Humans; D007248:Infertility, Male / Q000139:chemically induced* / Q000453:epidemiology / Q000235:genetics / Q000652:urine; D008297:Male; D018812:Paternal Exposure / Q000009:adverse effects; D011084:Polycyclic Aromatic Hydrocarbons / Q000032:analysis / Q000494:pharmacology / Q000633:toxicity* / Q000652:urine; D011110:Polymorphism, Genetic / Q000187:drug effects / Q000502:physiology; D011721:Pyrenes / Q000032:analysis; D012189:Retrospective Studies; D055101:Semen Analysis; D013094:Spermatozoa / Q000187:drug effects* / Q000378:metabolism
D018736:DNA Adducts; D011084:Polycyclic Aromatic Hydrocarbons; D011721:Pyrenes; C095911:polycyclic aromatic hydrocarbons-DNA adduct; D045643:DNA Repair Enzymes; C033146:1-hydroxypyrene