The placenta is the gateway between the mother and the developing fetus. Placental dysfunction can impair fetal growth and induce long-term effects in the progeny, including increased risk for metabolic diseases. The delicate balance of feto-maternal communication / exchange can be affected by a number of factors including maternal diet and diseases and / or exposure to endocrine disrupting compounds (EDCs). EDCs are synthetic or natural chemicals that interfere with the normal function of the endocrine system with some EDCs having steroidal activity. Fetal exposure to such EDCs can pose a threat to adult well-being. Current policy regulations are limiting the use of one of such EDCs, bisphenol A (BPA), in the manufacture process of consumer products. Emergence of new, untested, industrial chemical substitutes such as bisphenol S (BPS), an EDC with very distinct steroid affinities compared to BPA, are on the rise. Understanding the health risks posed by emerging EDC exposures is critical. Our preliminary studies using sheep as an in vivo model and in vitro studies using human cytotrophoblasts demonstrate that BPS exposure alters placental trophoblast function. BPA does not lead to a similar placental phenotype, highlighting critical and unexplored differences among bisphenolic EDCs. Our preliminary data suggest that BPS mediates its action via the progesterone receptor pathway. In our animal model, gestational BPS exposure also impacts fetal size and leads to cardio-metabolic disruptions. Studies described in this proposal will capitalize on a unique animal model of feto-maternal communication, primary trophoblast cells and trophoblast cell lines to test a novel hypothesis for the developmental origin of cardio-metabolic disorders with specific emphasis on understanding the molecular mechanisms whereby BPS compromises trophoblast function placental function and long-term cardio- metabolic effects on the progeny.

Public Health Relevance

During pregnancy, optimal maternal-placental-fetal communication is essential for maternal survival and fetal well-being. Gestational exposure to endocrine disrupting chemicals (EDCs) and can affect both, placental health and the developing fetus. The aim of this proposal is to understand the mechanisms by which bisphenol S disrupts placental trophoblastic function and progeny cardio- metabolic outcomes using in vivo and in vitro approaches.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES027863-03
Application #
9926259
Study Section
Systemic Injury by Environmental Exposure (SIEE)
Program Officer
Schug, Thaddeus
Project Start
2018-08-15
Project End
2023-05-31
Budget Start
2020-06-01
Budget End
2021-05-31
Support Year
3
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Michigan State University
Department
Veterinary Sciences
Type
Earth Sciences/Resources
DUNS #
193247145
City
East Lansing
State
MI
Country
United States
Zip Code
48824
Gingrich, Jeremy; Pu, Yong; Ehrhardt, Richard et al. (2018) Toxicokinetics of bisphenol A, bisphenol S, and bisphenol F in a pregnancy sheep model. Chemosphere 220:185-194