Maternal co-exposure to polystyrene microplastics and DEHP impairs thyroid function in adult rat offspring.

Maternal combined exposure to polystyrene microplastics (PS-MPs) and di-(2-ethylhexyl) phthalate (DEHP) poses potential risks to offspring endocrine development; however, the combined effects of these two contaminants remain poorly characterized. Pregnant rats were exposed to PS-MPs, DEHP, or a combination of both throughout pregnancy and lactation. The hypothalamic-pituitary-thyroid (HPT) axis function and gut microbiota composition were then assessed in adult offspring. Single-contaminant exposure altered thyroid hormone levels and HPT axis gene expression. Co-exposure exacerbated these disruptions, producing greater TSH suppression, elevated thyroid hormone levels, and uniform downregulation of Nis expression in offspring of both sexes. Sex-specific differences in hypothalamic and pituitary gene expression were observed, suggesting that upstream HPT axis regulation was disrupted via sex-divergent mechanisms. The combined exposure also induced morphological disruption of thyroid follicular epithelial cells and elevated oxidative stress markers. In co-exposed offspring, gut microbiome profiling revealed Bacteroides depletion and Enterococcus enrichment as the most prominent taxa-level shifts. The parallel perturbations in gut microbiome composition and HPT axis function across treatment groups support a proposed disruption model of the gut-brain-thyroid axis. Our findings demonstrate that maternal co-exposure to PS-MPs and DEHP induces sex-divergent thyroid endocrine disruption in offspring, driven by a complex integration of additive and synergistic toxicities. Consequently, relying exclusively on single-pollutant models likely underestimates the developmental health threats of real-world plastic mixtures, highlighting the critical need to incorporate mixture interactions and sex-specific vulnerabilities into future environmental risk assessments.