Investigating the effects of bisphenol a on the human placenta

Abstract

Introduction: Endocrine disrupting chemicals are environmental toxicants that humans are exposed to. Bisphenol A is classified as an endocrine disrupting chemical with xenoestrogenic capacity. The placenta is one of the least researched human organs, although it is crucial for the development of the embryo and fetus, and abnormal placental physiology can cause gestational complications that can lead to pregnancy determination. As such, we have elucidated the effects of bisphenol A in physiologically relevant doses on placental cell lines as well as human placental cells Methods: qPCR, Western blot, immunofluorescence, image stream, ELISA, microarray, 3D cell culture. Results: In placental cell lines BeWo and JEG-3, estrogen receptor a was the predominant receptor (p>0.001) in both non-syncytialised BeWo cells and in JEG-3 cells. 3 nM BPA treatment significantly increased cell proliferation in BeWo cells compared to controls (p<0.05), and this increase in cell proliferation was most likely due upregulation of estrogen receptor a (p<0.001) via a pathway involving p-p38 or p-AKT. Using microarray, pathways involving development of metabolic diseases such as type II diabetes, obesity and hypertension were significantly enriched in both the BeWo cell line and human placental cells after bisphenol A treatment. Finally, 3D models for placental culture were tested, showing that the 3D environment produces more physiologically relevant models of the human placenta, and methods prolonging the life of placental explants to up to 16 days were successfully developed. Conclusion: Bisphenol A in physiologically relevant doses changes the physiology of the human placenta via an upregulation of estrogen receptor a, causing an increase of cell proliferation and upregulating pathways that may result in the development of metabolic diseases, possibly exerting effects as early as fetal development. 3D models of human placenta should be used as a more physiologically relevant model of the human placenta when investigating these issues further.