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 5 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 (b 5 20.015, P 5 0.150) and 0.012 kg (b 5 20.012, P 5 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. Environ. Mol. Mutagen. 56:286-292, 2015Mutagen. 56:286-292, . V C 2014 Wiley Periodicals, Inc.

Background:No study has examined the association between prenatal phthalate exposure and intrauterine growth retardation (IUGR). This study aimed to investigate whether prenatal exposure to phthalates was associated with increased risk of IUGR. Methods: A total of 126 mother-newborn pairs, including 42 IUGR cases and 84 control newborns and their mothers, were enrolled in this case-control study. Spot urine samples were collected during the third trimester of pregnancy, and 5 phthalate metabolites (mono-n-butyl phthalate (MBP), monomethyl phthalate (MMP), mono-2-ethylhexyl phthalate (MEHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP)) were measured. results: Concentrations of MMP, MEHHP, MEOHP, and SumDEHP (MEHP, MEHHP, and MEOHP) were significantly higher in IUGR cases than in normal controls. In all subjects, urinary concentrations of MEHHP and MEOHP were significantly inversely associated with fetal growth indicators (birth weight and Quetelet's index). When mothers were stratified by infant sex, MEHHP and MEOHP concentrations were still negatively associated with fetal growth indicators, while no significant association was observed in females. In addition, exposureresponse relationships were observed between MEHHP/ SumDEHP concentrations in maternal urine and IUGR. conclusion: Prenatal exposure to phthalates was associated with increased risk of IUGR, and male newborns were more sensitive to phthalates than females. Phthalates, diesters of phthalic acid, are a group of chemicals that are widely used as plasticizers in many applications, including medical devices, toys, food wraps, shoe soles, and interior building surfaces (1). Because phthalates are additives and, as such, noncovalently bound to the plastic, they leach from the products with time and use, thus becoming ubiquitous environmental contaminants (2). Humans can be exposed to phthalates through inhalation, ingestion, dermal exposure, and medical treatments (3).Once taken into the body, phthalates are metabolized to their respective monoesters within a few hours or days, and then glucuronidated and excreted in the urine and feces. A notable human burden of phthalates has been reported and the consensus is that phthalate metabolites in urine could be used for assessing phthalate exposure in humans (4-11). In most cases, it is the monoester metabolites that have been claimed to be responsible for adverse health effects (12,13).Because phthalates can penetrate the placenta in humans (14), high phthalate levels in general, and in pregnant women in particular, have raised the urgent issue of prenatal exposure to phthalates. Fetuses are specifically vulnerable to a variety of toxicants because of the immaturity of their developing immune systems and the rapid development of their organs (15,16). During the fetal period, there is a "critical window" for the development of cardiovascular, nervous, reproductive, endocrine, immune, and respiratory systems when even a subtle exposure to chemicals may adverse...

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