Semen damage contributed over 50 % to air-pollutant-induced infertility: A prospective cohort study of 3940 men in China

Objective: To investigate the contribution of ambient air pollutants-induced semen damage to infertility risk, after iden-tifying dose-response relationship between pollutants and semen parameters and susceptibility window. Methods: In Preconception Reproductive Health and Birth Outcomes Cohort, 3940 male volunteers aged 22-49 were recruited from November 2018 to April 2021. At enrollment, resident address information was obtained and semen parameters were examined. During prospective follow-up, infertility was defined as failure to achieve pregnancy after unprotected intercourse within 12 months. Full coverage of ambient pollutant (PM2.5, PM10, SO2, NO2, O3, CO) concentrations was estimated by machine learning algorithms and assigned to individual level. Association be-tween pollutants and semen parameters was analyzed by single-and two-pollutant linear regression. Four potential sus-ceptibility windows were analyzed: lag 0-9d, lag 10-14d, lag 70-90d and lag 0-90d. Pollutant joint effects on semen parameters were analyzed by Bayesian kernel machine regression. Mediating effect of semen parameters on the asso-ciation between pollutants and infertility was analyzed. False-positive rate was controlled by Bonferroni correction.Results: Single-and two-pollutant models showed SO2, O3, PMs and NO2 were negatively associated with progressive motility, total motility and sperm morphology, among which, each IQR increase in SO2 at lag 0-90d was associated with -4.13 %(95%CI:-6.25 %, -1.95 %, P < 0.001) change of normal morphology, and O3 at lag 0-90d was nega-tively associated with progressive motility and total motility (f3 = -3.64 %, 95%CI:-5.63 %, -1.61 %; f3 = -2.24 %, 95%CI:-3.38 %, -1.08 %, P < 0.001). Joint effect analysis showed a negative effect on sperm concentration and a suggestive effect on vitality. Mediating effect analysis showed sperm normal morphology had a substantial me-diating effect in the association of SO2 with infertility (59.68 %, P < 0.001). Conclusion: Multiple air pollutants may introduce semen quality in the population at entire window of spermatogenesis, among which SO2 needs especial attention, as its damage on sperm morphology may increase risk of infertility.

Automated summary

This study investigated the contribution of ambient air pollutants-induced semen damage to infertility risk by identifying the dose-response relationship between pollutants and semen parameters and susceptibility window. The results showed that multiple air pollutants, including SO2, O3, PMs, and NO2, were negatively associated with progressive motility, total motility, and sperm morphology. The analysis also revealed a mediating effect of sperm normal morphology in the association between SO2 and infertility. These findings suggest that air pollutants may affect semen quality and increase the risk of infertility.