Genetic and Epigenetic Profiles of Polycystic Ovarian Syndrome and In Vitro Bisphenol Exposure in a Human Granulosa Cell Model
Reem Sabry,
Jenna F. Gallo,
Charlie Rooney,
Olivia L. M. Scandlan,
Ola S. Davis,
Shilpa Amin,
Mehrnoosh Faghih,
Megan Karnis,
Michael S. Neal,
Laura A. Favetta
Affiliations
Reem Sabry
Reproductive Health and Biotechnology Laboratory, Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada
Jenna F. Gallo
Reproductive Health and Biotechnology Laboratory, Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada
Charlie Rooney
Reproductive Health and Biotechnology Laboratory, Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada
Olivia L. M. Scandlan
Reproductive Health and Biotechnology Laboratory, Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada
Ola S. Davis
Reproductive Health and Biotechnology Laboratory, Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada
Shilpa Amin
ONE Fertility, Burlington, ON L7N 3T1, Canada
Mehrnoosh Faghih
ONE Fertility, Burlington, ON L7N 3T1, Canada
Megan Karnis
ONE Fertility, Burlington, ON L7N 3T1, Canada
Michael S. Neal
ONE Fertility, Burlington, ON L7N 3T1, Canada
Laura A. Favetta
Reproductive Health and Biotechnology Laboratory, Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada
Higher levels of bisphenols are found in granulosa cells of women with polycystic ovary syndrome (PCOS), posing the question: Is bisphenol exposure linked to PCOS pathophysiology? Human granulosa cells were obtained from women with and without PCOS, and genes and microRNAs associated with PCOS were investigated. The first phase compared healthy women and those with PCOS, revealing distinct patterns: PCOS subjects had lower 11β-HSD1 (p = 0.0217) and CYP11A1 (p = 0.0114) levels and elevated miR-21 expression (p = 0.02535), elucidating the molecular landscape of PCOS, and emphasizing key players in its pathogenesis. The second phase focused on healthy women, examining the impact of bisphenols (BPA, BPS, BPF) on the same genes. Results revealed alterations in gene expression profiles, with BPS exposure increasing 11β-HSD1 (p = 0.02821) and miR-21 (p = 0.01515) expression, with the latest mirroring patterns in women with PCOS. BPA exposure led to elevated androgen receptor (AR) expression (p = 0.0298), while BPF exposure was associated with higher levels of miR-155. Of particular interest was the parallel epigenetic expression profile between BPS and PCOS, suggesting a potential link. These results contribute valuable insights into the nuanced impact of bisphenol exposure on granulosa cell genes, allowing the study to speculate potential shared mechanisms with the pathophysiology of PCOS.
