Abstract
BackgroundIn recent years, oxidative stress has been studied extensively as a main contributing factor to male infertility. Nitric Oxide, a highly reactive free radical gas, is potentially detrimental to sperm function and sperm DNA integrity at high levels. Thus, the aim of this study was to investigate the associations between five polymorphisms in nitric oxide synthase genes (NOSs) and the risk of male infertility and sperm DNA damage as well.MethodsGenotypes were determined by the OpenArray platform. Sperm DNA fragmentation was detected using the Tdt-mediated dUTP nick-end labeling assay, and the level of 8-hydroxydeoxyguanosine (8-OHdG) in sperm DNA was measured using immunofluorescence. The adjusted odds ratio (OR) and 95% confidence interval (CI) were estimated using unconditional logistic regression.ResultsOur results revealed a statistically significant difference between the cases and controls in both genotypic distribution (P<0.001) and allelic frequency (P = 0.021) only for the NOS3 rs1799983 SNP. Multivariate logistic regression analyses revealed that rs1799983 was associated with a borderline significantly increased risk of male infertility (GT vs. GG: adjusted OR = 1.30, 95% CI: 1.00–1.70; GT+TT vs. GG: adjusted OR = 1.34, 95% CI: 1.03–1.74; P trend = 0.020). Moreover, NOS3 rs1799983 was positively associated with higher levels of sperm DNA fragmentation (β = 0.223, P = 0.044). However, the other 4 polymorphisms (NOS1 rs2682826, NOS1 rs1047735, NOS2 rs2297518, and NOS2 rs10459953) were not found to have any apparent relationships with male infertility risk.ConclusionsOf five NOS gene polymorphisms investigated in the present study, we found NOS3 rs1799983 might cause oxidative sperm DNA damage, thereby contributing to male infertility.
Highlights
Infertility is a common reproductive disorder that affects approximately one in six couples globally and male factors account for 40 to 50% of all infertile cases [1, 2]
Of five nitric oxide synthase genes (NOSs) gene polymorphisms investigated in the present study, we found NOS3 rs1799983 might cause oxidative sperm DNA damage, thereby contributing to male infertility
There was a significant difference between cases and controls with respect to semen concentration and sperm motility (37.9¡13.49% versus 65.3¡12.52%, P,0.001), but not semen volume (P50.809)
Summary
Infertility is a common reproductive disorder that affects approximately one in six couples globally and male factors account for 40 to 50% of all infertile cases [1, 2]. Though the aetiologies are still poorly understood, oxidative stress has been shown to be associated with impaired sperm motility and male infertility [3, 4]. Nitric Oxide, a highly reactive free radical gas, is potentially detrimental to sperm function and sperm DNA integrity at high levels. The aim of this study was to investigate the associations between five polymorphisms in nitric oxide synthase genes (NOSs) and the risk of male infertility and sperm DNA damage as well. Multivariate logistic regression analyses revealed that rs1799983 was associated with a borderline significantly increased risk of male infertility (GT vs GG: adjusted OR51.30, 95% CI: 1.00–1.70; GT+TT vs GG: adjusted OR51.34, 95% CI: 1.03–1.74; Ptrend50.020). NOS3 rs1799983 was positively associated with higher levels of sperm DNA fragmentation (b50.223, P50.044). The other 4 polymorphisms (NOS1 rs2682826, NOS1 rs1047735, NOS2 rs2297518, and NOS2 rs10459953) were not found to have any apparent relationships with male infertility risk
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