Effects of the endocrine disrupting chemical bisphenol A (BPA) in human placentation in vitro

Endocrine disrupting chemicals (EDCs) are environmental chemicals/toxicants that humans and wildlife are exposed to and which interfere with the action of hormones. Bisphenol A (BPA) is classified as an EDC with xenoestrogenic activity and is recognized by the WHO as a chemical with potentially potent effects on humans throughout different phases of development. A significant knowledge gap still exists regarding the complete spectrum of BPA-induced effects on human physiology, particularly on the placenta. As such, the present studies examined the effects of physiologically relevant doses BPA in vitro, using BeWo cells a well-characterised human placental cell line model. Treatment of BeWo cells with 3 nM BPA, induced cell proliferation and increased phosphorylation of p38. When treating BeWo cells with ER antagonists, there was a significant decrease in proliferation over 24 h when cells were treated with G15 (a GPR30 antagonist) and a moderate decrease when treated with the ERα antagonist ICI 182 780. Furthermore, microarray analysis identified 1195 genes that were differentially regulated in 3 nM BPA-treated BeWo cells. Most upregulated genes include: cytoplasmatic polyadenylation element-binding protein 1 (CPEB1), Myosin Light Chain 3 (MYL3), Caveolin-1 (CAV1), Calsyntenin-3 (CLSTN3), Hydroxycarboxylic acid receptor 3 (HCAR3), Serpin B9 (SERPINB9), Alanine-glyoxylate aminotransferase 2 (AGXT2), Transmembrane protein 45B (TMEM45B) and Eukaryotic translation initiation factor 4E type 2 (EIF4E2). Top 10 pathways associated with differentially expressed genes using Enrichr software, included leptin and insulin signalling, differentiation of white and brown adipocyte and integrin-mediated cell adhesion. Collectively our data provide a new insight of functions of BPA at placental level and provide a potential link with metabolic changes that can impact on the developing fetus.