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Investigating the effects of bisphenol a on the human placenta
This thesis was submitted for the award of Doctor of Philosophy and was awarded by Brunel University LondonIntroduction: 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
Is There a Link between Bisphenol A (BPA), a Key Endocrine Disruptor, and the Risk for SARS-CoV-2 Infection and Severe COVID-19?
Infection by the severe acute respiratory syndrome (SARS) coronavirus-2 (SARS-CoV-2) is the causative agent of a new disease (COVID-19). The risk of severe COVID-19 is increased by certain underlying comorbidities, including asthma, cancer, cardiovascular disease, hypertension, diabetes, and obesity. Notably, exposure to hormonally active chemicals called endocrine-disrupting chemicals (EDCs) can promote such cardio-metabolic diseases, endocrine-related cancers, and immune system dysregulation and thus, may also be linked to higher risk of severe COVID-19. Bisphenol A (BPA) is among the most common EDCs and exerts its effects via receptors which are widely distributed in human tissues, including nuclear oestrogen receptors (ERα and ERβ), membrane-bound oestrogen receptor (G protein-coupled receptor 30; GPR30), and human nuclear receptor oestrogen-related receptor gamma. As such, this paper focuses on the potential role of BPA in promoting comorbidities associated with severe COVID-19, as well as on potential BPA-induced effects on key SARS-CoV-2 infection mediators, such as angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). Interestingly, GPR30 appears to exhibit greater co-localisation with TMPRSS2 in key tissues like lung and prostate, suggesting that BPA exposure may impact on the local expression of these SARS-CoV-2 infection mediators. Overall, the potential role of BPA on the risk and severity of COVID-19 merits further investigation