Exposure to Phthalate, an Endocrine Disrupting Chemical, Alters the First Trimester Placental Methylome and Transcriptome in Women

Abstract Phthalates are known endocrine disruptors and associated with decreased fecundity, pregnancy loss, and adverse obstetrical outcomes, however the underlying mechanisms remain to be established. Environmental factors can influence gene expression and cell function by modifying epigenetic mark...

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Autores principales:	N. M. Grindler, L. Vanderlinden, R. Karthikraj, K. Kannan, S. Teal, A. J. Polotsky, T. L. Powell, I. V. Yang, T. Jansson
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/44c9ca0dfe614aea9075b7b4c26648fc
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spelling	oai:doaj.org-article:44c9ca0dfe614aea9075b7b4c26648fc2021-12-02T15:08:40ZExposure to Phthalate, an Endocrine Disrupting Chemical, Alters the First Trimester Placental Methylome and Transcriptome in Women10.1038/s41598-018-24505-w2045-2322https://doaj.org/article/44c9ca0dfe614aea9075b7b4c26648fc2018-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-24505-whttps://doaj.org/toc/2045-2322Abstract Phthalates are known endocrine disruptors and associated with decreased fecundity, pregnancy loss, and adverse obstetrical outcomes, however the underlying mechanisms remain to be established. Environmental factors can influence gene expression and cell function by modifying epigenetic marks, impacting the developing embryo as well as future generations of offspring. The impact of phthalates on placental gene methylation and expression is largely unknown. We studied the effect of maternal phthalate exposure on the human placental DNA methylome and transcriptome. We determined epigenome-wide DNA methylation marks (Illumina Infinium Human Methylation 850k BeadChip) and gene expression (Agilent whole human genome array) associated with phthalate exposure in first trimester placenta. Integrative genomic analysis of candidate genes was performed to define gene methylation-expression relationships. We identified 39 genes with significantly altered methylation and gene expression in the high phthalate exposure group. Most of these relationships were inversely correlated. This analysis identified epidermal growth factor receptor (EGFR) as a critical candidate gene mediating the effects of phthalates on early placental function. Although additional studies are needed to determine the functional consequences of these changes, our findings are consistent with the model that phthalates impact placental function by modulating the expression of critical placental genes through epigenetic regulation.N. M. GrindlerL. VanderlindenR. KarthikrajK. KannanS. TealA. J. PolotskyT. L. PowellI. V. YangT. JanssonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-9 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q N. M. Grindler L. Vanderlinden R. Karthikraj K. Kannan S. Teal A. J. Polotsky T. L. Powell I. V. Yang T. Jansson Exposure to Phthalate, an Endocrine Disrupting Chemical, Alters the First Trimester Placental Methylome and Transcriptome in Women
description	Abstract Phthalates are known endocrine disruptors and associated with decreased fecundity, pregnancy loss, and adverse obstetrical outcomes, however the underlying mechanisms remain to be established. Environmental factors can influence gene expression and cell function by modifying epigenetic marks, impacting the developing embryo as well as future generations of offspring. The impact of phthalates on placental gene methylation and expression is largely unknown. We studied the effect of maternal phthalate exposure on the human placental DNA methylome and transcriptome. We determined epigenome-wide DNA methylation marks (Illumina Infinium Human Methylation 850k BeadChip) and gene expression (Agilent whole human genome array) associated with phthalate exposure in first trimester placenta. Integrative genomic analysis of candidate genes was performed to define gene methylation-expression relationships. We identified 39 genes with significantly altered methylation and gene expression in the high phthalate exposure group. Most of these relationships were inversely correlated. This analysis identified epidermal growth factor receptor (EGFR) as a critical candidate gene mediating the effects of phthalates on early placental function. Although additional studies are needed to determine the functional consequences of these changes, our findings are consistent with the model that phthalates impact placental function by modulating the expression of critical placental genes through epigenetic regulation.
format	article
author	N. M. Grindler L. Vanderlinden R. Karthikraj K. Kannan S. Teal A. J. Polotsky T. L. Powell I. V. Yang T. Jansson
author_facet	N. M. Grindler L. Vanderlinden R. Karthikraj K. Kannan S. Teal A. J. Polotsky T. L. Powell I. V. Yang T. Jansson
author_sort	N. M. Grindler
title	Exposure to Phthalate, an Endocrine Disrupting Chemical, Alters the First Trimester Placental Methylome and Transcriptome in Women
title_short	Exposure to Phthalate, an Endocrine Disrupting Chemical, Alters the First Trimester Placental Methylome and Transcriptome in Women
title_full	Exposure to Phthalate, an Endocrine Disrupting Chemical, Alters the First Trimester Placental Methylome and Transcriptome in Women
title_fullStr	Exposure to Phthalate, an Endocrine Disrupting Chemical, Alters the First Trimester Placental Methylome and Transcriptome in Women
title_full_unstemmed	Exposure to Phthalate, an Endocrine Disrupting Chemical, Alters the First Trimester Placental Methylome and Transcriptome in Women
title_sort	exposure to phthalate, an endocrine disrupting chemical, alters the first trimester placental methylome and transcriptome in women
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/44c9ca0dfe614aea9075b7b4c26648fc
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Exposure to Phthalate, an Endocrine Disrupting Chemical, Alters the First Trimester Placental Methylome and Transcriptome in Women

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