Genetic and Epigenetic Profiles of Polycystic Ovarian Syndrome and In Vitro Bisphenol Exposure in a Human Granulosa Cell Model
-
Published:2024-01-21
Issue:1
Volume:12
Page:237
-
ISSN:2227-9059
-
Container-title:Biomedicines
-
language:en
-
Short-container-title:Biomedicines
Author:
Sabry Reem1ORCID, Gallo Jenna F.12, Rooney Charlie1, Scandlan Olivia L. M.1, Davis Ola S.1, Amin Shilpa23, Faghih Mehrnoosh23, Karnis Megan23, Neal Michael S.23ORCID, Favetta Laura A.1ORCID
Affiliation:
1. Reproductive Health and Biotechnology Laboratory, Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada 2. ONE Fertility, Burlington, ON L7N 3T1, Canada 3. Department of Obstetrics and Gynecology, McMaster University, Hamilton, ON L8S 4L8, Canada
Abstract
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.
Funder
Natural Sciences and Engineering Research Council of Canada General Purpose Grant Ontario Veterinary College Ontario Graduate Scholarships Department of Biomedical Sciences at the University of Guelph
Subject
General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)
Reference45 articles.
1. Polycystic Ovary Syndrome: Etiology, Pathogenesis and Diagnosis;Goodarzi;Nat. Rev. Endocrinol.,2011 2. Diagnostic Criteria for Polycystic Ovary Syndrome: Pitfalls and Controversies;Lujan;J. Obstet. Gynaecol. Can.,2008 3. Granulosa Cells and Follicular Development: A Brief Review;Cavalcanti;Rev. Assoc. Med. Bras.,2023 4. Marques, P., Skorupskaite, K., Rozario, K.S., Anderson, R.A., and George, J.T. (2022). Endotext, MDText.com, Inc. 5. Chaudhari, N., Dawalbhakta, M., and Nampoothiri, L. (2018). GnRH Dysregulation in Polycystic Ovarian Syndrome (PCOS) Is a Manifestation of an Altered Neurotransmitter Profile. Reprod. Biol. Endocrinol., 16.
|
|