| Objective:Declining semen quality and male infertility are global public health problems,and about half of all male infertility can be attributed to abnormal semen quality.An increasing number of studies have found a strong association between ambient air pollution and male reproductive health.Based on this,this study evaluated the dose-response relationships between ambient air pollutants(PM10、PM2.5、SO2、O3、NO2、CO)and semen parameters,the relationship between air pollutant exposure levels and infertility risk in men of reproductive age,and the potential critical susceptibility window.The role of semen damage in mediating the association between air pollutants and infertility risk was further investigated.Methods:In Preconception Reproductive Health and Birth Outcomes Cohort,men of childbearing age for pre-pregnancy health examination in Chongqing Maternal and Child Health Hospital were recruited from November 2018 to April 2021 to establish baseline.The address information and population characteristics of residents were obtained through questionnaire survey.Semen samples were collected at enrollment and semen parameters were examined.During prospective follow-up(once every three months),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.Daily exposure level of air pollutants at each subject’s residential address during the 3 months prior to enrollment(the reproductive cycle)was evaluated.Association between pollutants and semen parameters and the key susceptibility window were analyzed by single-pollutant linear regression.The effects of air pollutant exposure on male infertility and the key susceptibility window were analyzed by Logistic regression single pollutant model.And the sensitivity analysis was carried out by two-pollutants model.Four potential susceptibility windows were analyzed:lag 0-9d,lag 10-14d,lag 70-90d and lag 0-90d.Pollutant joint effects on semen parameters and infertility risk were analyzed by Bayesian kernel machine regression.Mediating effect of semen parameters on the association between pollutants and infertility was analyzed.False-positive rate was controlled by Bonferroni correction.Results:A total of 3,940 male subjects were included in the study.After multiple-test correction,single-and double-pollutant models showed that SO2,O3,PMs and NO2 were negatively associated with progressive motility,total motility and sperm morphology,among which,each IQR increase in SO2 at 0-90d window was associated with-4.13%(95%CI:-6.25%～-1.95%,P<0.001)change of normal morphology,and O3 at 0-90d window was negatively associated with progressive motility and total motility(β=-3.64%,95%CI:-5.63%～-1.61%,P<0.001;β=-2.24%,95%CI:-3.38%～-1.08%,P<0.001).Logistic regression model showed that the relative risk of infertility increased by 29.3%(RR=1.293,95%CI:1.022～1.636,P=0.008)when the highest and lowest quartiles of PM10 exposure were compared during 090d days before collect samples.The result of analysis for key susceptibility windows showed that PM10 was associated with infertility at all stages from 0-90 days,and no significant susceptibility window was observed.BKMR results showed that semen parameters,in particular sperm concentration and total sperm number,were negatively associated with air pollutant mixtures during the 0-90 days and 70-90 days windows before semen collection.No statistically significant results were observed in the analysis of the combined effect and interaction of air pollutants on infertility.Mediating effect analysis showed that normal sperm morphology had a substantial mediating effect(59.68%,P<0.001)on the SO2-infertility association.Conclusions:Our results suggest that multiple air pollutants may introduce damage to semen quality in the population at entire time window of spermatogenesis,PM10 exposure in men may increase the relative risk of infertility,and The damage of SO2 to sperm morphology may lead to the increase of male infertility risk. |
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