Abstract
Chlorpyrifos, one of the most widely used pesticides, can penetrate the placenta and affect fetal growth and neurodevelopment. Epigenetic regulation of peroxisome proliferator-activated receptor gamma (PPARγ), such as DNA methylation and trimethylation of lysine 4 of H3 (H3K4me3), may provide a potential mechanism for how fetal growth and development are impacted by chlorpyrifos exposure. The aims of the study were to investigate whether prenatal chlorpyrifos exposure was associated with H3K4me3 and DNA methylation levels of the PPARγ gene in the placenta and the related effects on birth outcomes and neurodevelopment. Among 425 mother-infant pairs from the Taiwan Birth Panel Study, chlorpyrifos levels were measured in cord blood by using online SPE-LC/HESI/MS/MS; placental PPARγ H3K4me3 and DNA methylation levels were measured by ChIP-qPCR and pyrosequencing, respectively; the neonates' health outcomes were extracted from the medical records; and childhood neurodevelopment was evaluated by using the Comprehensive Developmental Inventory for Infants and Toddlers in 2-year-old children. Multivariable regression models were used to adjust for potential confounders. After controlling for potential confounders, each unit increase in the natural log-transformed prenatal chlorpyrifos exposure level was associated with an increase in the PPARγ DNA methylation level (adjusted β (aβ)=0.77, p=0.032) and poorer performance in the cognitive and language domains at 2 years old, especially in boys (aβ=-1.66, p=0.016, and aβ=-1.79, p=0.023, respectively). PPARγ H3K4me3 levels were positively associated with gestational age (aβ=0.16, p=0.011), birth weight (aβ=30.52, p=0.013), birth length (aβ=0.18, p=0.003 and aβ=0.15, p=0.042), and gross-motor performance (aβ=1.67, p=0.036). Our findings suggested that prenatal chlorpyrifos exposure affected PPARγ DNA methylation levels and performance in the cognitive and language domains.
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