Prenatal chlorpyrifos exposure in association with PPARγ H3K4me3 and DNA methylation levels and child development

Background: 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 (PPAR gamma), 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 PPAR gamma gene in the placenta and the related effects on birth outcomes and neurodevelopment. Methods: 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 PPAR gamma 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. Results: After controlling for potential confounders, each unit increase in the natural log-transformed prenatal chlorpyrifos exposure level was associated with an increase in the PPAR gamma DNA methylation level (adjusted b (ab) = 0.77, p = 0.032) and poorer performance in the cognitive and language domains at 2 years old, especially in boys (ab = -1.66, p = 0.016, and ab = -1.79, p = 0.023, respectively). PPAR gamma H3K4me3 levels were positively associated with gestational age (ab = 0.16, p = 0.011), birth weight (ab = 30.52, p = 0.013), birth length (ab = 0.18, p = 0.003 and ab = 0.15, p = 0.042), and gross-motor performance (ab = 1.67, p = 0.036). Conclusions: Our findings suggested that prenatal chlorpyrifos exposure affected PPAR gamma DNA methylation levels and performance in the cognitive and language domains. (C) 2021 Published by Elsevier Ltd.

Automated summary

The study revealed that prenatal chlorpyrifos exposure was associated with an increase in PPAR gamma DNA methylation levels and poorer performance in cognitive and language domains at 2 years old, especially in boys. Additionally, PPAR gamma H3K4me3 levels were positively associated with gestational age, birth weight, birth length, and gross-motor performance.