title: Prenatal phthalate exposure, infant growth, and global DNA methylation of human placenta.
abstract: Prenatal phthalate exposure has been shown to be associated with reduced fetal growth. Epigenetic changes such as DNA methylation might be a molecular mechanism through which phthalate exposure affects fetal growth. In this study, we examined associations between prenatal phthalate exposure, infant growth, and global DNA methylation in human placenta samples. We measured global DNA methylation of 119 subjects [55 fetal growth restriction (FGR) cases and 64 normal controls], as assessed by long interspersed nuclear element-1 (LINE-1) methylation, via quantitative polymerase chain reaction-pyrosequencing. Prenatal phthalate exposure was assessed by measuring maternal urinary phthalate metabolites concentrations using high-performance liquid chromatography-tandem mass spectrometry. Concentrations of mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono (2-ethyl-5-oxohexyl) phthalate (MEOHP), and SumDEHP (molar sum of MEHP, MEHHP, and MEOHP) were significantly higher in FGR cases than those in normal controls (P = 0.002, 0.003, and 0.002, respectively). Placental LINE-1 methylation were found to be positively associated with fetal birth weight standard deviation scores, and negatively associated with urinary phthalate metabolites concentrations (MEHHP and SumDEHP). Every natural-log unit increase in urinary concentrations of MEHHP and SumDEHP was associated with 0.015 (β = -0.015, P = 0.150) and 0.012 kg (β = -0.012, P = 0.167) decrease in birth weight mediated through LINE-1 methylation. These findings suggest that changes in placental LINE-1 methylation might be part of the underlying biological pathway between prenatal phthalate exposure and adverse fetal growth.
authors.affiliation: Department of Environmental Health, School of Public Health, Fudan University, Shanghai, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Hui-jing
authors.initials: HJ
authors.lastname: Shi
authors.forename: Chang-ming
authors.initials: CM
authors.lastname: Xie
authors.forename: Jiao
authors.initials: J
authors.lastname: Chen
authors.forename: Hannah
authors.initials: H
authors.lastname: Laue
authors.forename: Yun-hui
authors.initials: YH
authors.lastname: Zhang
mesh_terms: D016022:Case-Control Studies; D019175:DNA Methylation / Q000187:drug effects*; D005260:Female; D005317:Fetal Growth Retardation / Q000139:chemically induced*; D006801:Humans; D007223:Infant; D020084:Long Interspersed Nucleotide Elements / Q000187:drug effects; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D010795:Phthalic Acids / Q000378:metabolism / Q000633:toxicity* / Q000652:urine; D010920:Placenta / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced*
chemical_list: D010795:Phthalic Acids; C032279:phthalic acid
keywords: DNA methylation; fetal growth restriction; low birth weight; phthalate exposure