Prenatal organophosphate esters exposure impacts placental structure and inflammatory markers in a trimester-specific manner

Organophosphate esters (OPEs) are emerging environmental pollutants with potential neurotoxic effects, yet their associations with placental development remain poorly understood. In this study of 2,258 mother-child pairs from the Ma'anshan Birth Cohort, maternal urinary concentrations of tris(2-chloroethyl) phosphate (TCEP) and six OPE metabolites were measured across all three trimesters. We examined associations between these OPEs and eight placental structural/efficiency parameters as well as fourteen inflammation/stress markers. Generalized estimating equations with a sex interaction term were used to assess individual exposure effects. Quantile g-computation was applied to evaluate mixture effects, and a multiple informant model was used to capture trimester-specific associations. For placental structure and efficiency, exposure to BEHP was positively associated with placental thickness, with no trimester- and sex- specific effects observed. Regarding inflammation and stress markers, first-trimester BEHP exposure was linked to lower levels of several markers, including MCP-1, HO-1, HIF1-α, GRP78, IL-6 and CD68; first-trimester DBzP exposure was linked to lower levels of HO-1, HIF1-α, GRP78; second-trimester DBP exposure was linked to higher levels of HO-1, HIF1-α and GRP78. No clear sex-specific patterns were identified for these markers. Mixture analyses showed that first-trimester OPEs mixture exposure was associated with lower levels of HO-1, GRP78, and IL-6. These findings suggest that prenatal exposure to OPEs, particularly during early pregnancy, may be associated with alterations in placental development and immune regulation, with potential implications for long-term offspring health. Further studies are warranted to confirm these findings and clarify their biological relevance.