Low-level environmental arsenic exposure correlates with unexplained male infertility risk

Humans are exposed to arsenic via drinking water, dietary intake and inhaled particulates. Endemic chronic arsenic exposure related reproductive toxicity is well documented, but the effect of low-level general environmental arsenic exposure on unexplained male infertility (UMI) remains unclear. In this case-control study, we aimed to investigate the relationship between non-geogenic environmental arsenic exposure and UMI risk. One hundred and one infertile men with normal semen as cases and sixty one fertile men as controls were recruited. Five urinary arsenic species: pentavalent arsenate (Asi(V)), trivalent arsenite (Asi(III)), methylated to monomethylarsonic acid (MMA(V)), dimethylarsinic acid (DMA(V)), arsenobetaine (AsB) were quantitatively measured by liquid chromatography-inductively coupled plasma-mass spectrometry (LC-ICP-MS). To assess the semen quality, semen volume, sperm concentration, total motility, and progressive motility were measured. The nonparametric Mann-Whitney U test was used to compare the differences of arsenic species and index between the case and the control group; we observed that concentrations of Asi(V), AsB, MMA(V), DMA(V), total inorganic As and total As were significantly higher in the cases than the controls. The urine Asi(V) level increased more than twenty folds in case group. Moreover, higher redox index (Asi(V)/Asi(III)) and lower primary arsenic methylation index (PMI=MMA(V)/Asi) were observed for case group. Furthermore, through the logistic regression analysis, we observed that the urine Asi(V) level and PMI were most significantly associated with UMI risk among the observations. Specifically, in comparison to the first quartile, the subjects with higher Asi(V) levels were more likely to exhibit UMI with increasing adjusted odds ratios (AORs) (adjusted by age, body mass index, drinking status and smoking status) of 8.39 [95% confidence interval (CI), 2.59-27.17], 13.12 (95% CI, 3.44-50.12) and 36.51 (95% CI, 8.25-161.66) at the second, third and fourth quartiles, respectively. Also a concentration-dependent decrease of AOR was also observed for PMI in comparison to the fourth quartile: 15.43 [95% CI, 4.28-55.69], 9.69 (95% CI, 2.78-33.78) and 6.93 (95% CI, 2.21-21.76) at the first, second and third quartiles, respectively. These findings provide evidences that low-level environmental arsenic exposure was positively associated with UMI risk.