Bisphenol A exposure alters developmental gene expression in the fetal rhesus macaque uterus

Kathryn C Calhoun; Elizabeth Padilla-Banks; Wendy N Jefferson; Liwen Liu; Kevin E Gerrish; Steven L Young; Charles E Wood; Patricia A Hunt; Catherine A Vandevoort; Carmen J Williams

doi:10.1371/journal.pone.0085894

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Bisphenol A exposure alters developmental gene expression in the fetal rhesus macaque uterus

Journal article

Open access

Bisphenol A exposure alters developmental gene expression in the fetal rhesus macaque uterus

Kathryn C Calhoun, Elizabeth Padilla-Banks, Wendy N Jefferson, Liwen Liu, Kevin E Gerrish, Steven L Young, Charles E Wood, Patricia A Hunt, Catherine A Vandevoort and Carmen J Williams

PloS one, Vol.9(1), pp.e85894-e85894

2014

DOI: https://doi.org/10.1371/journal.pone.0085894

Handle:

https://hdl.handle.net/2376/113850

PMCID: PMC3900442

PMID: 24465770

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Abstract

Uterus - pathology

Oligonucleotide Array Sequence Analysis

Benzhydryl Compounds - toxicity

Fetal Development - drug effects

Maternal-Fetal Exchange

Phenols - toxicity

Uterus - drug effects

Uterus - metabolism

Gene Expression Regulation, Developmental - drug effects

Macaca mulatta

Receptors, Progesterone - genetics

Transcriptome - drug effects

Environmental Exposure

Gene Regulatory Networks

Uterus - embryology

Maternal Exposure

beta Catenin - metabolism

Endocrine Disruptors - toxicity

Receptors, Progesterone - metabolism

Pregnancy

Animals

Estrogen Receptor alpha - genetics

Estrogen Receptor alpha - metabolism

Female

Bisphenol A (BPA) exposure results in numerous developmental and functional abnormalities in reproductive organs in rodent models, but limited data are available regarding BPA effects in the primate uterus. To determine if maternal oral BPA exposure affects fetal uterine development in a non-human primate model, pregnant rhesus macaques carrying female fetuses were exposed orally to 400 µg/kg BPA or vehicle control daily from gestation day (GD) 50-100 or GD100-165. Fetal uteri were collected at the completion of treatment (GD100 or GD165); tissue histology, cell proliferation, and expression of estrogen receptor alpha (ERα) and progesterone receptor (PR) were compared to that of controls. Gene expression analysis was conducted using rhesus macaque microarrays. There were no significant differences in histology or in the percentage of cells expressing the proliferation marker Ki-67, ERα, or PR in BPA-exposed uteri compared to controls at GD100 or GD165. Minimal differences in gene expression were observed between BPA-exposed and control GD100 uteri. However, at GD165, BPA-exposed uteri had significant differences in gene expression compared to controls. Several of the altered genes, including HOXA13, WNT4, and WNT5A, are critical for reproductive organ development and/or adult function. We conclude that second or third trimester BPA exposure does not significantly affect fetal uterus development based on morphological, proliferation, and steroid hormone receptor assessments. However, differences in expression of key developmental genes after third trimester exposure suggest that BPA could alter transcriptional signals influencing uterine function later in life.

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Title: Bisphenol A exposure alters developmental gene expression in the fetal rhesus macaque uterus
Creators: Kathryn C Calhoun - Reproductive Medicine Group, Laboratory of Reproductive & Developmental Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, United States of America ; Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina, United States of America
Elizabeth Padilla-Banks - Reproductive Medicine Group, Laboratory of Reproductive & Developmental Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, United States of America
Wendy N Jefferson - Reproductive Medicine Group, Laboratory of Reproductive & Developmental Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, United States of America
Liwen Liu - Microarray Group, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, United States of America
Kevin E Gerrish - Microarray Group, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, United States of America
Steven L Young - Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina, United States of America
Charles E Wood - National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, North Carolina, United States of America
Patricia A Hunt - School of Molecular Biosciences, Washington State University, Pullman, Washington, United States of America
Catherine A Vandevoort - Department of Obstetrics and Gynecology and California National Primate Research Center, University of California Davis, Davis, California, United States of America
Carmen J Williams - Reproductive Medicine Group, Laboratory of Reproductive & Developmental Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, United States of America
Publication Details: PloS one, Vol.9(1), pp.e85894-e85894
Academic Unit: Molecular Biosciences, School of
Publisher: United States
Grant note: R01 ES013527 / NIEHS NIH HHS R01 ES016770 / NIEHS NIH HHS Intramural NIH HHS P51 OD011107 / NIH HHS P51 RR000169 / NCRR NIH HHS R01 HD067721 / NICHD NIH HHS ES016770 / NIEHS NIH HHS ES013527 / NIEHS NIH HHS R56 ES013527 / NIEHS NIH HHS ES102405 / NIEHS NIH HHS
Identifiers: 99900548221501842
Language: English
Resource Type: Journal article