Gestational exposure to BPA alters the expression of glucose and lipid metabolic mediators in the placenta: role in programming offspring for obesity

Archana Molangiri; Saikanth Varma; Navya Sree Boga; Priti Das; Asim K Duttaroy; Sanjay Basak

doi:10.1016/j.tox.2024.153957

Gestational exposure to BPA alters the expression of glucose and lipid metabolic mediators in the placenta: role in programming offspring for obesity

Toxicology. 2024 Sep 20:153957. doi: 10.1016/j.tox.2024.153957. Online ahead of print.

Authors

Archana Molangiri¹, Saikanth Varma¹, Navya Sree Boga¹, Priti Das¹, Asim K Duttaroy², Sanjay Basak³

Affiliations

¹ National Institute of Nutrition, Indian Council of Medical Research, Hyderabad, India; Molecular Biology Division, ICMR-National Institute of Nutrition, Indian Council of Medical Research, Hyderabad, India.
² Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway.
³ National Institute of Nutrition, Indian Council of Medical Research, Hyderabad, India; Molecular Biology Division, ICMR-National Institute of Nutrition, Indian Council of Medical Research, Hyderabad, India. Electronic address: sba_bioc@yahoo.com.

PMID: 39307384
DOI: 10.1016/j.tox.2024.153957

Abstract

Bisphenol A (BPA) exposure during pregnancy is known to predispose offspring to obesity in later life. Our previous studies demonstrated obesogenic effects in BPA-exposed offspring, including excess body fat, increased feed efficiency, adipocyte hypertrophy, and altered leptin signaling. However, the role of the placenta in mediating these effects remained unclear. This study investigates the mechanisms by which BPA exposure affects placental glucose and lipid transporters and their impact on offspring adiposity in Wistar rats. Dams were orally gavaged with BPA [0.4 (low dose-LD) and 4.0 (high dose-HD) μg/kg body weight] from gestational day (gD) 4 to 14. Gestational exposure to LD BPA increased the expression of 11β hydroxysteroid dehydrogenase 1 (11β HSD1) and estrogen receptor alpha (ERα) proteins (p<0.05) in the placenta compared to control and HD BPA. Similar changes were observed in the expression of mTOR signaling mediators, fatty acid transporters, and intracellular fatty acid-binding proteins. There were no changes in the dam's body weight or lipid and glucose profiles. However, there was a dose dependent increase in glucose transporter (GLUT1) expression in the placenta. While LD BPA increased hexokinase 2 expression in the placenta, HD BPA had no effect. Both doses of BPA increased IL6 expression, but only LD BPA exposure increased PPAR-gamma expression. Additionally, BPA exposure induced ADRP expression and localization, suggesting potential lipid overload in the placenta. Furthermore, BPA exposure altered the placental epigenetic profile, with increased expression of DNA methyltransferases (DNMTs). Overall, gestational BPA exposure led to dose-specific alterations in placental glucose and lipid metabolic activities, possibly playing an role in increasing the supply of these macronutrients to the fetus and predisposing the offspring to obesity.

Keywords: ADRP; BPA; Bisphenol; GLUT1; Obesogens; Placenta; mTOR.