Chung-Hsing Chen1, Shih Sheng Jiang2, I-Shou Chang3, Hui-Ju Wen4, Chien-Wen Sun4, Shu-Li Wang5. 1. National Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan; Taiwan Bioinformatics Core, National Health Research Institutes, Zhunan, Taiwan. 2. National Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan. Electronic address: ssjiang@nhri.org.tw. 3. National Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan; Taiwan Bioinformatics Core, National Health Research Institutes, Zhunan, Taiwan; Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan. 4. National Institute of Environmental Health Sciences, National Health Research Institutes, Zhunan, Taiwan. 5. National Institute of Environmental Health Sciences, National Health Research Institutes, Zhunan, Taiwan; School of Public Health, National Defense Medical Center, Taipei. Electronic address: slwang@nhri.org.tw.
Abstract
BACKGROUND: Phthalic acid esters are ubiquitous and antiandrogenic, and may cause systemic effects in humans, particularly with in utero exposure. Epigenetic modification, such as DNA methylation, has been hypothesized to be an important mechanism that mediates certain biological processes and pathogenic effects of in utero phthalate exposure. OBJECTIVE: The aim of this study was to examine the association between genome-wide DNA methylation at birth and prenatal exposure to phthalate. METHODS: We studied 64 infant-mother pairs included in TMICS (Taiwan Maternal and Infant Cohort Study), a long-term follow-up birth cohort from the general population. DNA methylation levels at more than 450,000 CpG sites were measured in cord blood samples using Illumina Infinium HumanMethylation450 BeadChips. The concentrations of three metabolites of di-(2-ethylhexyl) phthalate (DEHP) were measured using liquid chromatography tandem-mass spectrometry (LC-MS/MS) in urine samples collected from the pregnant women during 28-36 weeks gestation. RESULTS: We identified 25 CpG sites whose methylation levels in cord blood were significantly correlated with prenatal DEHP exposure using a false discovery rate (FDR) of 5% (q-value < 0.05). Via gene-set enrichment analysis (GSEA), we also found that there was significant enrichment of genes involved in the androgen response, estrogen response, and spermatogenesis within those genes showing DNA methylation changes in response to exposure. Specifically, PA2G4, HMGCR, and XRCC6 genes were involved in genes in response to androgen. CONCLUSIONS: Phthalate exposure in utero may cause significant alterations in the DNA methylation in cord blood. These changes in DNA methylation might serve as biomarkers of maternal exposure to phthalate in infancy and potential candidates for studying mechanisms via which phthalate may impact on health in later life. Future investigations are warranted.
BACKGROUND:Phthalic acid esters are ubiquitous and antiandrogenic, and may cause systemic effects in humans, particularly with in utero exposure. Epigenetic modification, such as DNA methylation, has been hypothesized to be an important mechanism that mediates certain biological processes and pathogenic effects of in utero phthalate exposure. OBJECTIVE: The aim of this study was to examine the association between genome-wide DNA methylation at birth and prenatal exposure to phthalate. METHODS: We studied 64 infant-mother pairs included in TMICS (Taiwan Maternal and Infant Cohort Study), a long-term follow-up birth cohort from the general population. DNA methylation levels at more than 450,000 CpG sites were measured in cord blood samples using Illumina Infinium HumanMethylation450 BeadChips. The concentrations of three metabolites of di-(2-ethylhexyl) phthalate (DEHP) were measured using liquid chromatography tandem-mass spectrometry (LC-MS/MS) in urine samples collected from the pregnant women during 28-36 weeks gestation. RESULTS: We identified 25 CpG sites whose methylation levels in cord blood were significantly correlated with prenatal DEHP exposure using a false discovery rate (FDR) of 5% (q-value < 0.05). Via gene-set enrichment analysis (GSEA), we also found that there was significant enrichment of genes involved in the androgen response, estrogen response, and spermatogenesis within those genes showing DNA methylation changes in response to exposure. Specifically, PA2G4, HMGCR, and XRCC6 genes were involved in genes in response to androgen. CONCLUSIONS:Phthalate exposure in utero may cause significant alterations in the DNA methylation in cord blood. These changes in DNA methylation might serve as biomarkers of maternal exposure to phthalate in infancy and potential candidates for studying mechanisms via which phthalate may impact on health in later life. Future investigations are warranted.
Authors: Youssef Oulhote; Bruce Lanphear; Joseph M Braun; Glenys M Webster; Tye E Arbuckle; Taylor Etzel; Nadine Forget-Dubois; Jean R Seguin; Maryse F Bouchard; Amanda MacFarlane; Emmanuel Ouellet; William Fraser; Gina Muckle Journal: Environ Health Perspect Date: 2020-02-19 Impact factor: 9.031
Authors: Rebekah L Petroff; Vasantha Padmanabhan; Dana C Dolinoy; Deborah J Watkins; Joseph Ciarelli; Diana Haggerty; Douglas M Ruden; Jaclyn M Goodrich Journal: Front Genet Date: 2022-03-31 Impact factor: 4.772