Introduction/Background Bisphenols (BPs) are endocrine disrupting chemicals identified as contaminants of concern for reproductive toxicity. Currently, commonly used are bisphenol S (BPS) and F (BPF) that can be detected in human body fluids. We have established that both BPS and BPF affect cell cycle distribution and steroidogenic activity of human ovarian granulosa cells. Another process that can be affected by BPs is cell death. Apoptosis plays a crucial role in the pathogenesis of ovarian cancer, polycystic ovary syndrome (PCOS) and other ovarian diseases. In granulosa cells apoptosis predominantly occurs via caspase-dependent signaling pathways. Therefore, here we studied impact of BPs on cell death by researching how BPS and BPF would affect effector caspases activity.

Methodology Human non-luteinised granulosa cell line (HGrC1) was used as in vitro model to investigate the effects of BPs. The cells were treated with 0.1, 1, 10 and 100 nM BPS or BPF for 24h prior to analysis of DNA content and caspase activity and with 10 nM for 6h prior to flow cytometry analysis. For real-time apoptotic progression test cells were treated with BPs (10 nM) and monitored up to 24h.

Results We have established that BPs do not have an effect on DNA content and apoptosis but do have impact on caspases, mainly by lowering caspase-9 activity in HGrC1 cells.

Conclusion Caspase-9 is directly linked to mitochondrial-centered cell death, therefore, we suggest that BPs by lowering caspase-9 desensitize ovarian granulosa cells to apoptosis and trigger non-apoptotic pathways. Caspase-9 is often connected to the execution of cell differentiation, and its non-apoptotic functions are increasingly being linked to cancer and other ovarian diseases pathogenesis. These studies highlight the importance of caspase 9 activity in granulosa cells functions and suggest that research into regulation of cell death may be the key to understanding development of female reproductive system dysfunctions.

Disclosures This research has been funded by the program ’Excellence Initiative – Research University’ at the Jagiellonian University.