ArticleEnvironmental health : a global access science source2026
Placental CYP450 gene dysregulation by maternal PFAS: a novel mechanism linking prenatal exposure to altered toddler growth.
Article in Environmental health : a global access science source, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundMaternal per- and polyfluoroalkyl substances (PFAS) exposure has been linked to adverse health effects on offspring, but the mechanisms remain unclear. The present study investigates the relationship between maternal PFAS exposure and the expression of placental cytochrome P450 enzymes (CYP19A1, CYP2J2, and CYP2E1), and explores the potential role of these enzymes in linking maternal PFAS exposure to offspring development.
methodsWe included 350 mother-infant pairs from the Jiashan birth cohort. Thirteen PFAS compounds were measured in maternal plasma collected at 8-16 weeks of gestation, while the expression levels of the three CYP genes were quantified in placental tissues collected at delivery. Offspring weight and length were measured at birth and at 1, 3, 6, 8, 12, and 24 months of age, and their ponderal index (PI) was computed. Multivariable linear regression was used to examine associations between plasma concentrations of individual PFAS and placental CYP gene expression. Quantile-based g-computation was used to examine the association of the PFAS mixture with placental CYP gene expression. A linear mixed model was used to examine the associations of maternal PFAS and placental CYP expression levels with repeated PI measurements from birth to 24 months. Multilevel mediation analysis was conducted to explore the potential mediating role of CYP genes.
resultsConsistent inverse associations between maternal PFAS exposure and the three placental CYP genes expression in female placentas were observed. Specifically, statistically significant decreases were observed in the associations between all PFAS compounds and CYP2J2 expression with β- estimates for the highest exposure versus the lowest from -0.255 to -0.174, as well as between the highest exposure of perfluorotridecanoic acid (PFTrDA) and CYP19A1 expression (β = -0.279, 95% CI: -0.55, -0.007). In contrast, for male fetuses, significant associations were found between the highest exposure of perfluorohexane sulfonate (PFHxS) and increased CYP19A1 expression (β = 0.404, 95%CI: 0.131,0.677), and between the middle of perfluoroundecanoic acid (PFUdA), perfluorododecanoic acid (PFDoA), PFTrDA, and perfluoroheptanoic acid (PFHPA) and decreased CYP2E1 expression (β
conclusionsThese results indicate that maternal PFAS exposure may disrupt placental CYP expression and the implications of these disruptions for offspring development warrant further investigation.
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