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Prenatal exposure to phthalates and peripheral blood and buccal epithelial DNA methylation in infants: An
Gillian England-Mason1, Sarah M Merrill2, Nicole Gladish2
1Department of Paediatrics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Owerko Centre, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada.
Insights
Prenatal phthalate exposure is linked to DNA methylation changes in infant blood and buccal cells, potentially impacting genes related to hormones, immunity, and neurodevelopment.
Area of Science:
- Environmental Epigenetics
- Developmental Toxicology
- Human Health Risk Assessment
Background:
- Prenatal exposure to phthalates is associated with adverse health and neurodevelopmental outcomes.
- DNA methylation (DNAm) alterations are a potential mechanism, but studies are limited to placental tissue and umbilical cord blood.
- Investigating DNAm in accessible infant tissues is crucial for understanding phthalate effects.
Purpose of the Study:
- To conduct an epigenome-wide association study (EWAS) of phthalate exposure and DNAm in infant venous buffy coat blood and buccal epithelial cells (BECs).
- To identify specific DNA methylation changes associated with prenatal phthalate exposure in accessible infant tissues.
- To explore the role of DNAm as a mediator of phthalate-induced health effects.
Main Methods:
- Analyzed maternal urine for phthalate metabolites from 152 mother-infant pairs.
- Collected infant blood or BECs at 3 months for DNAm profiling using the Infinium HumanMethylation450 BeadChip.
- Employed robust linear regressions to assess associations between phthalate metabolites and DNAm at CpG sites, adjusting for confounders.
Main Results:
- Replicated a previously identified CpG in RNF39 associated with prenatal phthalate exposure.
- Identified 12 high-confidence CpGs in infant blood and 12 in BECs associated with high and/or low molecular weight phthalates.
- Observed associations between prenatal bisphenol A (BPA) exposure and two CpGs linked to high molecular weight phthalates in BECs.
Conclusions:
- Prenatal phthalate exposure is associated with DNAm variations in infant blood and BECs.
- Affected genes are involved in endocrine hormone activity, immune pathways, DNA damage, and neurodevelopment.
- Further research is needed to confirm these findings in larger cohorts and across tissues, and to link them to health outcomes.
Background:
Prenatal exposure to phthalates has been associated with adverse health and neurodevelopmental outcomes. DNA methylation (DNAm) alterations may be a mechanism underlying these effects, but prior investigations of prenatal exposure to phthalates and neonatal DNAm profiles are limited to placental tissue and umbilical cord blood.
Objective:
Conduct an epigenome-wide association study (EWAS) of the associations between prenatal exposure to phthalates and DNAm in two accessible infant tissues, venous buffy coat blood and buccal epithelial cells (BECs).
Methods:
Participants included 152 maternal-infant pairs from the Alberta Pregnancy Outcomes and Nutrition (APrON) study. Maternal second trimester urine samples were analyzed for nine phthalate metabolites. Blood (n = 74) or BECs (n = 78) were collected from 3-month-old infants and profiled for DNAm using the Infinium HumanMethylation450 (450K) BeadChip. Robust linear regressions were used to investigate the associations between high (HMWPs) and low molecular weight phthalates (LMWPs) and change in methylation levels at variable Cytosine-phosphate-Guanine (CpG) sites in infant tissues, as well as the sensitivity of associations to potential confounders.
Results:
One candidate CpG in gene RNF39 reported by a previous study examining prenatal exposure to phthalates and cord blood DNAm was replicated. The EWAS identified 12 high-confidence CpGs in blood and another 12 in BECs associated with HMWPs and/or LMWPs. Prenatal exposure to bisphenol A (BPA) associated with two of the CpGs associated with HMWPs in BECs.
Discussion:
Prenatal exposure to phthalates was associated with DNAm variation at CpGs annotated to genes associated with endocrine hormone activity (i.e., SLCO4A1, TPO), immune pathways and DNA damage (i.e., RASGEF1B, KAZN, HLA-A, MYO18A, DIP2C, C1or109), and neurodevelopment (i.e., AMPH, NOTCH3, DNAJC5). Future studies that characterize the stability of these associations in larger samples, multiple cohorts, across tissues, and investigate the potential associations between these biomarkers and relevant health and neurodevelopmental outcomes are needed.
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