Transgenerational and endocrine-disrupting effects of polylactic acid MPs and bisphenol TMC in zebrafish: A sex-specific study.

Bisphenol TMC (BPTMC), a novel bisphenol A substitute, is widely used as a plastic additive and frequently co-occurs with microplastics (MPs) in various environmental media. Their coexistence may alter biological effects, adding complexity to environmental risk assessment. This study investigated the reproductive and transgenerational toxicity of BPTMC and polylactic acid (PLA) MPs on zebrafish, both individually and in combination, focusing on sex-specific endocrine-disrupting mechanisms. Both BPTMC and PLA impaired gonadal function and germ cell development. BPTMC exhibited sex-specific endocrine disruption, significantly increasing 17β-estradiol in males while decreasing it in females, alongside a more pronounced reduction in testosterone in males. Parental exposure also induced transgenerational developmental toxicity in F1 offspring, including increased mortality and malformations, reduced heart rate, and decreased body length. These effects were linked to the dysregulation of key hypothalamic-pituitary-gonadal axis genes (gnrh3, fshβ, cyp19a1a, esr2a, esr2b). Molecular docking further confirmed that BPTMC activates Esr2a and Esr2b, contributing to reproductive dysfunction. Notably, co-exposure to PLA mitigated BPTMC toxicity, likely by adsorbing BPTMC, reducing its aqueous concentration by 35 % and lowering its bioavailability. This study offers new insights into the biological interactions between plastic additives and MPs, enhancing our understanding of the combined ecological risks posed by emerging contaminants.