Delineating potential effects of Bisphenol A on placental fatty acid homeostasis
Abstract
Placental essential fatty acid (EFA) homeostasis represents a delicate yet highly complex process required for guiding proper pregnancy and fetal outcomes. Numerous transcriptional regulators, fatty acid transport proteins, and metabolizing enzymes function in concert to establish an adequate balance in fatty acid transport and metabolic activities that ultimately determine placental EFA homeostasis. Therefore, discrepancies in these systems can potentially impair EFA homeostasis and compromise pregnancy outcomes and/or fetal development. Previous results from our laboratory have shown that exposure of pregnant rats to the endocrine disrupting chemical (EDC) Di-(2-ethylhexyl)-phthalate (DEHP) and its metabolites can dramatically alter the expression of fatty acid transporters and metabolizing enzymes in the rat placenta and subsequently lead to a significant reduction in transplacental EFA transfer and changes in the fetal brain lipid metabolome. This thesis focuses on the potential effects of Bisphenol A (BPA), an EDC often used in conjunction with DEHP and recently linked to lipid imbalance conditions, on placental fatty acid homeostasis using the in vitro rat HRP-1 trophoblastic model. Our current observations demonstrate that physiologically relevant doses of BPA induce significant changes in the genotypic and phenotypic expression of several fatty acid homeostasis associated isoforms in exposed HRP-1 trophoblasts. In addition, BPA induces significant functional effects in EFA uptake and transport kinetics pertinent to governing EFA transfer across the placenta. Our findings, thus, are suggestive that BPA may disrupt placental EFA transfer, and are particularly significant due to the fact that the low dose of 50 nM BPA used in our studies is consistent with levels normally observed in human placental tissues and maternal plasma. If our observations were to be proven true in future in vivo correlative studies, it would indicate that an imbalance in placental and fetal EFA homeostasis would arise leading to potential adverse pregnancy and/or fetal outcomes. Considering that over 15% of pregnancies suffer from lipid imbalance complications, our findings serve to justify further in vivo investigations with the overarching goal of determining the potential implications of BPA, alone or in combination with other xenobiotics, in adverse pregnancy and/or fetal outcomes characterized by discrepancies in lipid homeostasis. Taken together, our focus on the effects of BPA on placental fatty acid homeostasis represents an area of tremendous significance that still remains largely unexplored with particular clinical relevance as EDCs are ever increasing in the environment and exposure risks to the highly susceptible pregnant women population grow exponentially.
Degree
Ph.D.
Advisors
Knipp, Purdue University.
Subject Area
Medicine|Pharmacy sciences
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