Bisphenol-A Analogue (bisphenol-S) Exposure Alters Female Reproductive Tract and Apoptosis/oxidative Gene Expression in Blastocyst-derived Cells

Objectives: One of the major endocrine-disrupting chemicals, bisphenol-S (BPS) has replaced bisphenol-A due to public health anxiety. The present study evaluated low dosage BPS effect on female reproductive potential, hormonal disruption, and gene expression pathways of blastocyst-derived cells.

Materials And Methods: NMRI female mice (5-6 weeks) in the estrous stage were chosen following vaginal smear examination for estrus cycle detection and BPS (0, 1, 5, 10, 50 and 100 µg/kg) was administrated subcutaneously for twenty-one consecutive days. After the last administration, blood, ovary tissue and oocytes were collected for further examination.

Results: BPS induced oxidative stress in ovarian tissue and reduced hormonal status, LH and FSH, even at low concentration. Furthermore, apoptosis was induced in blastocyst derived cells in BPS administrated mice groups even at low BPS concertation, however, P53 and E2f1 expression were downregulated in doses more than 50 µg/kg, which might indicate apoptosis pathway exchange from P53 dependent to p53 independent pathways. IVF outcome was negatively associated with blastocyst apoptosis gene expression, estrogen receptor beta (ERβ) as well as oxidative status in ovaries. Finally, Stepwise regression indicated that E2f1, Nrf2, catalase (CAT), and malondialdehyde (MDA) could be chosen as predictor values for hatch percentage in IVF outcome.

Conclusion: In summary, this study revealed BPS might have detrimental potential in the female reproductive system by oxidation induction and hormonal alteration as well as next generation blastocyst derived cells apoptosis induction. Further studies are recommended for public health assurance of BPS safety especially for female consumed products.