Co-exposure of phthalates, bisphenols, parabens, and polycyclic aromatic hydrocarbons in follicular fluid of women undergoing assisted reproductive technologies and the associations with hormone levels

Endocrine-disrupting chemicals (EDCs), particularly phthalates (PAEs), bisphenols, parabens, and polycyclic aromatic hydrocarbons (PAHs), constitute pervasive environmental contaminants with demonstrated potential to adversely affect female reproductive health. Although these compounds are known to exert adverse effects, critical knowledge gaps persist concerning their specific associations with reproductive outcomes. The present study analyzed 144 follicular fluid samples from women undergoing assisted reproductive technology procedures, quantifying concentrations of PAE metabolites (mPAEs), bisphenols, parabens, and hydroxylated PAHs (OH-PAHs). Analytical results demonstrated a descending concentration gradient: mPAEs exhibited the highest median concentration (6.14 ng/mL), followed by parabens (2.17 ng/mL), bisphenols (1.33 ng/mL), and OH-PAHs (0.26 ng/mL). Notably, the study identified a positive correlation between follicular fluid bisphenol concentrations and testosterone levels, along with a potential association between PAE exposure and elevated risk of secondary infertility. Application of Bayesian kernel machine regression and Quantile g-computation models revealed that EDCs predominantly influence hormone levels through mixture effects, with increasing chemical mixture concentrations corresponding to decreased estradiol levels on hCG trigger day and reduced basal progesterone. The models specifically identified bisphenol S (BPS) and bisphenol P (BPP) as the predominant mediators of these endocrine disruptions, respectively, suggesting that bisphenols may disrupt female reproductive health through endocrine interference mechanisms.