Prenatal Nutrition Containing Bisphenol A Affects Placenta Glucose Transfer: Evidence in Rats and Human Trophoblast

Abstract

This work aims to clarify the effect of dietary supplementation with Bisphenol A (BPA), a chemical widely present in beverage and food containers, on placental glucose transfer and pregnancy outcome. The study was performed on female Sprague Dawley rats fed with a diet containing BPA (2.5, 25 or 250 μg/Kg/day) for a period of a month (virgin state) plus 20 days during pregnancy. Western blot analysis and immunohistochemistry were performed in placental tissues for glucose type 1 transporter (GLUT1). Furthermore, human trophoblast, HTR8-SV/neo cells, were used to evaluate the effect of BPA on glucose transport and uptake. Studies in rats showed that food supplementation with BPA, produces a higher fetal weight (FW) to placenta weight (PW) ratio at the lowest BPA concentration. Such low concentrations also reduced maternal weight gain in late pregnancy and up-regulated placental expression of GLUT1. Treatment of HTR8-SV/neo with the non-toxic dose of 1 nM BPA confirmed up-regulation of GLUT1 expression and revealed higher activity of the transporter with an increase in glucose uptake and GLUT1 membrane translocation. Overall, these results indicate that prenatal exposure to BPA affects pregnancy and fetal growth producing changes in the placental nutrients-glucose transfer.

Placental Glucose Transporters and Response to Bisphenol A in Pregnancies from of Normal and Overweight Mothers

“…The explants were then subjected to RNA and protein extraction followed by qPCR and a WB analysis for the transporters GLUT1 and GLUT4 as described in the material and method section. In line with the findings in the trophoblast cells [ 14 ], GLUT1 protein expression was significantly increased ( p < 0.05; Fold Change 2.200) in placenta explants by BPA treatment. Similarly, the effect was obtained at 1 nM, while 1 μM was ineffective.…”

“…First of all, we observed, in explants obtained from NW women, an increase in GLUT1 expression as a result of exposure to BPA. The increase in GLUT1 levels was observed at low doses of the endocrine disrupter (environmentally relevant dose), confirming data by Benincasa et al and Rajakumar et al [ 14 , 47 ]. On the other hand, we detected a dose-dependent decrease in the expression of GLUT1 in placenta explants from OW women after exposure to the endocrine disrupter.…”

“…Studies carried out by Benincasa et al showed an increase in GLUT1 levels in a human trophoblast cell line treated with BPA [ 14 ]. To explore if the endocrine disruptor could have the same effect on our in vitro model, the placental explants from physiological pregnancies of NW women were treated with BPA at two different concentrations (1 nm and 1 μm) or vehicle as control (Ct).…”

“…The study showed changes in fetal and placental weight leading to higher fetal growth and an increased placental expression of GLUT-1. Upregulation of GLUT1 expression and glucose transfer was also shown in human trophoblast cells [ 14 ]. Glucose is one of the main nutrients for fetal development.…”

Bisphenol S Impairs Invasion and Proliferation of Extravillous Trophoblasts Cells by Interfering with Epidermal Growth Factor Receptor Signaling

“…Particularly concerning are exposures that occur during pregnancy, since bisphenol chemicals can not only reach and target the developing fetus [ 19 ], but also the placenta [ 2 ]. BPA [ 20 , 21 , 22 ] and, more recently, BPS have been reported to affect placental morphology, cell fusion, and nutrient transport [ 16 , 22 , 23 , 24 ].…”