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Updated: Aug 15, 2025
Assessment and Evaluation of the High Risk Neonate: The NICU Network Neurobehavioral Scale
Published on: August 25, 2014
Networks of placental DNA methylation correlate with maternal serum PCB concentrations and child neurodevelopment
Julia S Mouat1, Xueshu Li2, Kari Neier1
1Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, CA, USA; Perinatal Origins of Disparities Center, University of California, Davis, CA, USA; Genome Center, University of California, Davis, CA, USA; MIND Institute, University of California, Davis, CA, USA.
Insights
Gestational exposure to polychlorinated biphenyls (PCBs) is linked to neurodevelopmental disorders. Placental DNA methylation patterns associated with maternal PCB levels and child neurodevelopmental outcomes, particularly involving CSMD1 and AUTS2, were identified.
Area of Science:
- Environmental epigenetics
- Neurodevelopmental disorder research
- Placental biology
Background:
- Gestational exposure to polychlorinated biphenyls (PCBs) is associated with increased neurodevelopmental disorder risk.
- Placental epigenetics, specifically DNA methylation, may mediate this risk or indicate altered placental function.
- Previous studies linked placental DNA methylation to maternal PCB exposure and autism spectrum disorder (ASD) risk, but lacked whole-genome sequencing data for simultaneous analysis.
Purpose of the Study:
- To identify placental DNA methylation patterns associated with maternal PCB levels and child neurodevelopmental outcomes.
- To investigate potential epigenetic mechanisms linking gestational PCB exposure to neurodevelopmental outcomes in a high-risk cohort.
Main Methods:
- Analysis of 209 PCB congeners in maternal serum samples from 104 participants.
- Identification of placental DNA methylation networks using whole genome bisulfite sequencing and weighted gene correlation network analysis (Comethyl R package).
- Testing placental DNA methylation modules for associations with maternal PCB levels, child neurodevelopment, and participant traits.
Main Results:
- Five placental DNA methylation modules significantly correlated with one or more PCBs, and four correlated with child neurodevelopment.
- Two modules showed associations with both maternal PCB levels and child neurodevelopment, mapping to CSMD1 and AUTS2.
- CSMD1 and AUTS2 are genes previously implicated in ASD and differentially methylated in response to gestational PCB exposure in mouse models.
Conclusions:
- Placental DNA co-methylation modules are associated with maternal PCB exposure and child neurodevelopmental outcomes.
- Methylation patterns in CSMD1 and AUTS2 may serve as biomarkers for altered placental function and/or ASD risk following maternal PCB exposure.
Background:
Gestational exposure to polychlorinated biphenyls (PCBs) has been associated with elevated risk for neurodevelopmental disorders. Placental epigenetics may serve as a potential mechanism of risk or marker of altered placental function. Prior studies have associated differential placental DNA methylation with maternal PCB exposure or with increased risk of autism spectrum disorder (ASD). However, sequencing-based placental methylomes have not previously been tested for simultaneous associations with maternal PCB levels and child neurodevelopmental outcomes.
Objectives:
We aimed to identify placental DNA methylation patterns associated with maternal PCB levels and child neurodevelopmental outcomes in the high-risk ASD MARBLES cohort.
Methods:
We measured 209 PCB congeners in 104 maternal serum samples collected at delivery. We identified networks of DNA methylation from 147 placenta samples using the Comethyl R package, which performs weighted gene correlation network analysis for whole genome bisulfite sequencing data. We tested placental DNA methylation modules for association with maternal serum PCB levels, child neurodevelopment, and other participant traits.
Results:
PCBs 153 + 168, 170, 180 + 193, and 187 were detected in over 50% of maternal serum samples and were highly correlated with one another. Consistent with previous findings, maternal age was the strongest predictor of serum PCB levels, alongside year of sample collection, pre-pregnancy BMI, and polyunsaturated fatty acid levels. Twenty seven modules of placental DNA methylation were identified, including five which significantly correlated with one or more PCBs, and four which correlated with child neurodevelopment. Two modules associated with maternal PCB levels as well as child neurodevelopment, and mapped to CSMD1 and AUTS2, genes previously implicated in ASD and identified as differentially methylated regions in mouse brain and placenta following gestational PCB exposure.
Conclusions:
Placental DNA co-methylation modules were associated with maternal PCBs and child neurodevelopment. Methylation of CSMD1 and AUTS2 could be markers of altered placental function and/or ASD risk following maternal PCB exposure.
