Bisphenol S Impaired Human Granulosa Cell Steroidogenesis in Vitro

Abstract

Bisphenol S (BPS) is a structural analog of the endocrine disruptor bisphenol A (BPA); it is the main BPA replacement in the plastics industry. Previous studies have shown that BPA and BPS exhibit similar effects on reproduction in fish and rodent species. BPS reportedly alters steroidogenesis in bovine granulosa cells. Luteinised granulosa cells collected from 59 women who were undergoing an in vitro fertilization procedure were cultured for 48 h in the presence or absence of BPS (10 nM, 100 nM, 1 µM, 10 µM or 50 µM). BPS exposure was investigated by assessing follicular fluids from these 59 women for their BPS content. Culture medium, cells, total messenger RNA (mRNA) and total protein extracted from the luteinised granulosa cells were examined for oestradiol and progesterone secretion, cellular proliferation, viability, gene expression, steroidogenic enzyme expression and cell signaling. BPS was measured in follicular fluids using mass spectrometry. Exposure of granulosa cells to 10 or 50 µM BPS for 48 h induced a 16% (p = 0.0059) and 64% (p < 0.0001) decrease, respectively, in progesterone secretion; 50 µM BPS decreased oestradiol secretion by 46% (p < 0.0001). Ten µM BPS also tended to reduce CYP11A1 protein expression by 37% (p = 0.0947) without affecting HSD3B1 and CYP19A1 expression. Fifty µM BPS increased ERRγ expression. Environmental levels of BPS (nanomolar range) did not induce changes in steroidogenesis in human granulosa cells. The effects of BPS were observed after only 48 h of BPS exposure. These acute effects might be similar to chronic effects of physiological BPS levels.

BPA and BPS Affect Connexin 37 in Bovine Cumulus Cells

“…Isolating/culturing cumulus cells is a valuable complement to our previous experiments since it provides a model where controlled manipulation of cellular functions is possible. In vitro culture of cumulus cells has been extensively utilized in endocrine research as early as 1989 in rats [ 43 ], with particular focus on the effects of reproductive toxicants on these cellular processes [ 12 , 22 , 44 ]. Cumulus cells are quickly being recognized for their importance as experimental models as they offer a non-invasive approach to oocyte quality assessment and prediction of embryonic fates [ 45 ].…”

“…BPA and BPS very likely have different mechanisms of action and further research is required before an accurate conclusion on BPS safety can be made [ 64 , 65 , 66 ]. Teteau et al [ 12 ] and Amar et al [ 22 ] investigated the mechanism by which BPS can affect sheep and human granulosa cells, respectively. They reported that BPS does not affect cell viability or proliferation, which may explain why we did not see an observable change in flask confluency in the BPS group.…”

“…They reported that BPS does not affect cell viability or proliferation, which may explain why we did not see an observable change in flask confluency in the BPS group. Nevertheless, these studies do report that BPS impairs steroidogenesis with disruptions in estradiol and progesterone secretions and dysregulated gene expression of crucial steroidogenic genes [ 12 , 22 ]. This strengthens our indication that BPS may work through a different mechanism than BPA.…”

“…Moreover, BPS exposure disrupted oocyte maturation, decreased cumulus cell expansion and induced cytoskeletal disruption in pig oocytes [ 20 ]. Lastly, in more recent studies, BPS has also been reported to alter steroidogenic genes and pathways in sheep and human granulosa cells with an overall reduction in progesterone and estrogen secretion and a decrease in oocytes that reached maturation [ 21 , 22 ]. BPS is used as substitute in plastics, but there is a lack of research supporting their safety [ 23 ].…”

Endocrine Disrupting Chemicals: Current Understanding, New Testing Strategies and Future Research Needs

“…In ovines, BPS exposure impairs oocyte development competence with blastocyte rate reduction being observed [ 5 ]. In human granulosa cells, the administration of BPS leads to reduced secretion of oestradiol and progesterone which are observed after 48 h of exposure suggesting that the effects of chronic exposure might be similar [ 6 ]. As BPA crosses the placental barrier, and is known to have an effect on the expression of genes involved with fetal brain development, gene expression in the anterior hypothalamus was studied after exposure in mice highlighting the involvement particularly of genes that are currently thought to be key in Autism Spectrum Disorders [ 7 ].…”