What does this research mean for the field?

Maternal exposure to PFAS mixtures is associated with decreased expression of placental CYP450 enzymes in female fetuses, though these enzymes were not found to significantly mediate the relationship between prenatal PFAS exposure and toddler growth trajectories. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

This study aims to explore how maternal PFAS exposure affects the expression of placental CYP450 genes and subsequent toddler growth outcomes.

June 5, 2026Open Access

Placental CYP450 gene dysregulation by maternal PFAS: a novel mechanism linking prenatal exposure to altered toddler growth

Key Points

This study aims to explore how maternal PFAS exposure affects the expression of placental CYP450 genes and subsequent toddler growth outcomes.
Included 350 mother-infant pairs from the Jiashan birth cohort.
Measured 13 PFAS compounds in maternal plasma during gestation and quantified CYP gene expression in placental tissues at delivery.
Used multivariable linear regression and quantile-based g-computation to analyze the associations between PFAS levels and CYP gene expression.
PFAS mixture was linked to decreased expression of CYP19A1, CYP2J2, and CYP2E1 in placentas of female fetuses (β = -0.344, 95% CI: -0.571,-0.117).
Lower CYP19A1 expression correlated with reduced ponderal index (PI) in girls and increased PI in boys.
No significant mediating role of CYP19A1 between PFTrDA and PI in girls, or PFHxS and PI in boys.

Abstract

BACKGROUND: Maternal 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. METHODS: We 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. RESULTS: = -0.344, 95% CI: -0.571,-0.117, respectively). The PFAS mixture was associated with decreased the three CYP genes expression in the placenta of female fetuses, but no association was observed in male placentas. Additionally, placental CYP19A1 expression was associated with a decrease in girls' PI and an increase in boys' PI, respectively. However, no mediating role of CYP19A1 in the relationship between PFTrDA and PI in girls or between PFHxS and PI in boys was observed, as the indirect effect was not statistically significant. CONCLUSIONS: These results indicate that maternal PFAS exposure may disrupt placental CYP expression and the implications of these disruptions for offspring development warrant further investigation.

اسأل الذكاء الاصطناعي

Bookmark

View Full Paper