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

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Abstract

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 mg/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 (ERa) 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, ERa, 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.

Original languageEnglish (US)
Article numbere85894
JournalPLoS One
Volume9
Issue number1
DOIs
StatePublished - Jan 23 2014

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ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Calhoun, K. C., Padilla-Banks, E., Jefferson, W. N., Liu, L., Gerrish, K. E., Young, S. L., Wood, C. E., Hunt, P. A., VandeVoort, C. A., & Williams, C. J. (2014). Bisphenol A exposure alters developmental gene expression in the fetal rhesus macaque uterus. PLoS One, 9(1), [e85894]. https://doi.org/10.1371/journal.pone.0085894