Long-term effect of fine particulate matter constituents on reproductive hormones homeostasis in women attending assisted reproductive technologies: A population-based longitudinal study

Fine particulate matter (PM_2.5) may disrupt women's reproductive hormones, posing potential reproductive risks. However, the exact compositions of PM_2.5 responsible for these effects remain unclear. Our investigation explored the long-term impacts of PM_2.5 constituents on reproductive hormones, based on a large longitudinal assisted reproductive cohort study in Anhui, China. We included 24,396 reproductive hormone samples from 19,845 women attending assisted reproductive technologies (ART) between 2014 and 2020. Using high-resolution gridded data (1-km resolution), we calculated the residence-specified PM_2.5 constituents during the year before the month of hormone testing. Relationships between PM_2.5 constituents [organic matter (OM), chloride (Cl^-), sulfate (SO₄^2-), ammonium (NH₄⁺), black carbon, and nitrate] and reproductive hormones were investigated using the linear mixed model with subject-specific intercepts. The constituent-proportion model and the constituent-residual model were also constructed. Additionally, cubic spline analysis was used to examine the potential non-linear exposure-response relationship. We found that per interquartile range (IQR) increment in OM was associated with a 5.31 % (3.74 %, 6.89 %) increase in estradiol, and per IQR increment in Cl^- and NH₄⁺ were associated with 13.56 % (7.63 %, 19.82 %) and 9.07 % (4.35 %, 14.01 %) increases in luteinizing hormone. Conversely, per IQR increment in OM and Cl^- were associated with -7.27 % (-9.34 %, -5.16 %) and -8.52 % (-10.99 %, -5.98 %) decreases in progesterone, and per IQR increment in SO₄^2- was associated with a -9.15 % (-10.31 %, -7.98 %) decrease in testosterone. These associations were held in both proportional and residual models. Moreover, exposure-response curves for estradiol and progesterone with PM_2.5 constituents exhibited approximately U-shaped. These results suggested that specific PM_2.5 constituents might disrupt reproductive hormone homeostasis in women attending ART, providing new evidence for formulating PM_2.5 pollution reduction strategies that could benefit women's reproductive health.