Bisphenol A exposure alters developmental gene expression in the fetal rhesus macaque uterus.
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.
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.
Kathryn C
KC
Calhoun
Reproductive Medicine Group, Laboratory of Reproductive & Developmental Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, United States of America.
Elizabeth
E
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
WN
Jefferson
Microarray Group, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, United States of America.
Liwen
L
Liu
Microarray Group, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, United States of America.
Kevin E
KE
Gerrish
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.
Steven L
SL
Young
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.
Charles E
CE
Wood
School of Molecular Biosciences, Washington State University, Pullman, Washington, United States of America.
Patricia A
PA
Hunt
Department of Obstetrics and Gynecology and California National Primate Research Center, University of California Davis, Davis, California, United States of America.
Catherine A
CA
Vandevoort
Reproductive Medicine Group, Laboratory of Reproductive & Developmental Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, United States of America.
Carmen J
CJ
Williams
D000818:Animals; D001559:Benzhydryl Compounds / Q000633:toxicity*; D052244:Endocrine Disruptors / Q000633:toxicity*; D004781:Environmental Exposure; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D005260:Female; D047109:Fetal Development / Q000187:drug effects; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D053263:Gene Regulatory Networks; D008253:Macaca mulatta; D018811:Maternal Exposure; D008431:Maternal-Fetal Exchange; D020411:Oligonucleotide Array Sequence Analysis; D010636:Phenols / Q000633:toxicity*; D011247:Pregnancy; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome / Q000187:drug effects; D014599:Uterus / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism / Q000473:pathology; D051176:beta Catenin / Q000378:metabolism; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D047628:Estrogen Receptor alpha; D010636:Phenols; D011980:Receptors, Progesterone; D051176:beta Catenin; C006780:bisphenol A; D000098826:Bisphenol A Compounds