Female reproductive hormones link short-term air pollution exposure to compromised oocyte-related outcomes

The role of reproductive hormones in the associations of air pollution with oocyte-related outcomes remains unclear. In 6376 women undergoing assisted reproductive technology, we investigated the mediating role of reproductive hormones in the association between air pollutants during the 90 days pre-retrieval to gonadotropin start and oocyte-related outcomes. Results showed that nitrogen dioxide (NO₂) was negatively associated with prolactin (PRL) (β [95% confidence interval (CI)] = -0.049 [-0.078, -0.020]), and ozone (O₃) was negatively associated with luteinizing hormone (LH) (β [95% CI] = -0.064 [-0.093, -0.036]) and estradiol (E2) (β [95% CI] = -0.137 [-0.168, -0.106]). Furthermore, in the negative associations of air pollutant mixtures with hormones, O₃ was consistently identified as the predominant risk contributor. Additionally, E2 was negatively associated with all oocyte-related outcomes [β ranges: -0.088 to -0.072; all false discovery rate P (P-FDR) < 0.01], whereas LH and PRL showed significant positive associations (β ranges = 0.028-0.419; all P-FDR < 0.01). Mediation analysis, which relies on statistical assumptions, suggested that PRL may partially explain the association between NO₂ and total oocyte yield, and that LH and E2 may partially explain the association between O₃ and total and mature oocyte yields. Network toxicology predicted that air pollutants may disrupt hormone-related pathways (such as estrogen signaling pathways) by regulating genes such as TP53, EGFR, and MAPK, compromising female fertility. In conclusion, our study provides novel epidemiological evidence and mechanistic clues to the adverse reproductive risk of air pollution in females.