Declines in ovarian reserve associated with ambient ozone exposure: mediating role of lipid profile

BACKGROUND: Ambient ozone pollution represents a growing threat to public health. However, evidence regarding its association with ovarian reserve and the mediating mechanisms remains limited and inconsistent. METHODS: This cross-sectional study included 8,233 women aged 20-45 who attended the Center for Reproductive Medicine at Jiangxi Maternal and Child Health Hospital between 2021 and 2023. Based on data from the Tracking Air Pollution in China project, ozone exposure was determined by assigning 10-km-resolution daily maximum 8-hour average ozone concentration to each participant's residential address. Serum anti-Müllerian hormone (AMH) levels were measured to evaluate ovarian reserve, with six distinct exposure periods defined according to the stages of female follicular development. Participants' lipid profiles were characterized by total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol and triglycerides. The ozone-AMH relationship was assessed using multivariable linear regression models, supplemented by stratified, mediation, and sensitivity analyses. RESULTS: Each interquartile range increase in ozone concentration was linked to an 8.14% (95% confidence intervals [CI]: 3.09% to 12.93%) decrease in AMH levels during period 4. Compared with women aged 20-29 years, this ozone-related decline was less pronounced among women over 35 (P for interaction = 0.004). Among the four lipid indicators, TC mediated 11.415% of the association between ozone and AMH levels, while LDL-C accounted for 7.38%. Similar findings were observed for period 6, while no significant linear associations were identified across the other periods. CONCLUSION: Higher ambient ozone exposure is significantly linked to diminished ovarian reserve. This association is particularly evident during the developmental window from primary and secondary follicles to small antral follicle stage, with younger women showing greater susceptibility. To the best of current knowledge, this study provides the first evidence that alterations in lipid profiles may partially mediate this relationship, offering novel insights for protecting female reproductive health and informing environmental health interventions.