Abstract
Exposure to bisphenolic chemicals during pregnancy occurs in > 90% of pregnancies. Bisphenolic compounds can cross the placental barrier reaching fetal circulation. However, the effects of emerging bisphenolic compounds, such as bisphenol S (BPS), on placental function remain untested. The aim was to determine if bisphenol A (BPA) or BPS, at an environmentally relevant dose, impairs placental function. Pregnant sheep were randomly distributed into three treatment groups (n = 7–8/group): control, BPA, and BPS. All animals received daily injections of corn oil (control), BPA, or BPS (0.5 mg/kg; s.c.; internal fetal doses were ~ 2.6 ng/mL unconjugated BPA and ~ 7.7 ng/mL of BPS) from gestational day 30–100. After a 20-day washout period, placentas were weighed and placentomes collected. Placental endocrine function was assessed on biweekly maternal blood samples. Gestational exposure to BPS, but not BPA, reduced maternal circulating pregnancy-associated glycoproteins without change in placental weight or placental stereology. BPS-exposed placentas had 50% lower e-cadherin protein expression, ~ 20% fewer binucleate cells, and ~ threefold higher glial cell missing-1 protein expression. BPA placentas were not affected highlighting the intrinsic differences among bisphenolic chemicals. This is the first study to demonstrate that gestational BPS can result in placental endocrine dysfunction and points to a dysregulation in the fusogenic trophoblast signaling pathway.
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Acknowledgements
We thank Michigan State University (MSU) Sheep Teaching and Research Farm for help with animal husbandry, Dr. Ramona Ehrhardt for help with fetal catheterization, the MSU Diagnostic Center for Population and Animal Health for help with biochemistry analyses, Ms. Lindsay Hannah and Ms. Gabriela Saldana for their help during animal experimentation, and Ms. Madilyn Johnson for help with stereological analyses of the placenta.
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Research reported in this publication was supported by the National Institute of Environmental Health Sciences of the National Institute of Health (1K22ES026208 to AV-L), Michigan State University (MSU), MSU AgBioResearch, and the United States Department of Agriculture (USDA) National Institute of Food and Agriculture (Hatch MICL02383). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
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Gingrich, J., Pu, Y., Roberts, J. et al. Gestational bisphenol S impairs placental endocrine function and the fusogenic trophoblast signaling pathway. Arch Toxicol 92, 1861–1876 (2018). https://doi.org/10.1007/s00204-018-2191-2
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DOI: https://doi.org/10.1007/s00204-018-2191-2