Urinary Metabolic Biomarkers Link Oxidative Stress
Indicators Associated with General Arsenic Exposure to Male Infertility
In a Han Chinese Population
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Abstract
To
investigate the hypothesis that general environmental arsenic
(As) exposure can impair male fertility, we designed a case-control
study examining possible correlations between the concentrations of
different As species in urine [controls (<i>n</i> = 151)
vs cases (<i>n</i> = 140)], urinary metabolic biomarkers
[controls (<i>n</i> = 158) vs cases (<i>n</i> =
135)], and infertility characterized by poor semen quality. Regional
participants were recruited sequentially from the affiliated hospitals
of Nanjing Medical University. Elevated inorganic arsenate (As<sub>i</sub><sup>V</sup>) exposure was associated with infertility: in
comparison with the first quartile, subjects with As<sub>i</sub><sup>V</sup> levels above the median were more likely to exhibit male
idiopathic infertility with increasing adjusted odds ratios (AOR)
of 4.9 [95% confidence interval (CI), 1.8β13.6] and 13.6 (95%
CI, 4.8β38.6) at the third and fourth quartiles (<i>P</i> = 0.000 for trend), respectively. Other As species did not exhibit
a significant dose-dependent correlation with infertility risk. Levels
of urinary biomarkers correlated with both male infertility and As<sub>i</sub><sup>V</sup> concentrations [controls (<i>n</i> =
145) vs cases (<i>n</i> = 123)]; the latter correlation
was independent of disease. These included acylcarnitines, aspartic
acid, and hydroxyestrone, which were negatively associated with infertility,
and uridine and methylxanthine, which were positively associated.
In conclusion, for the first time we show that elevated urinary concentrations
of As<sub>i</sub><sup>V</sup> from general As exposure are significantly
associated with male infertility, and As species may exert toxicity
via oxidative stress and sexual hormone disrupting mechanisms, as
indicated by related biomarkers