Matthew W Woods1,2, Muhammad Atif Zahoor1,2, Sara Dizzell1,2, Chris P Verschoor1,3, Charu Kaushic1,2. 1. Department of Pathology and Molecular Medicine, Michael G. DeGroote Center for Learning and Discovery, McMaster University, Hamilton, ON, Canada. 2. McMaster Immunology Research Center, Michael G. DeGroote Center for Learning and Discovery, McMaster University, Hamilton, ON, Canada. 3. McMaster Institute for Research on Aging, McMaster Innovation Park, McMaster University, Hamilton, ON, Canada.
Abstract
PROBLEM: Medroxyprogesterone acetate (MPA), a progestin-based hormonal contraceptive designed to mimic progesterone, has been linked to increased human immunodeficiency virus (HIV-1) susceptibility. Genital epithelial cells (GECs) form the mucosal lining of the female genital tract (FGT) and provide the first line of protection against HIV-1. The impact of endogenous sex hormones or MPA on the gene expression profile of GECs has not been comprehensively documented. METHOD OF STUDY: Using microarray analysis, we characterized the transcriptional profile of primary endometrial epithelial cells grown in physiological levels of E2, P4, and MPA. RESULTS: Each hormone treatment altered the gene expression profile of GECs in a unique manner. Interestingly, although MPA is a progestogen, the gene expression profile induced by it was distinct from P4. MPA increased gene expression of genes related to inflammation and cholesterol synthesis linked to innate immunity and HIV-1 susceptibility. CONCLUSION: The analysis of gene expression profiles provides insights into the effects of sex hormones and MPA on GECs and allows us to posit possible mechanisms of the MPA-mediated increase in HIV-1 acquisition.
PROBLEM: Medroxyprogesterone acetate (MPA), a progestin-based hormonal contraceptive designed to mimic progesterone, has been linked to increased humanimmunodeficiency virus (HIV-1) susceptibility. Genital epithelial cells (GECs) form the mucosal lining of the female genital tract (FGT) and provide the first line of protection against HIV-1. The impact of endogenous sex hormones or MPA on the gene expression profile of GECs has not been comprehensively documented. METHOD OF STUDY: Using microarray analysis, we characterized the transcriptional profile of primary endometrial epithelial cells grown in physiological levels of E2, P4, and MPA. RESULTS: Each hormone treatment altered the gene expression profile of GECs in a unique manner. Interestingly, although MPA is a progestogen, the gene expression profile induced by it was distinct from P4. MPA increased gene expression of genes related to inflammation and cholesterol synthesis linked to innate immunity and HIV-1 susceptibility. CONCLUSION: The analysis of gene expression profiles provides insights into the effects of sex hormones and MPA on GECs and allows us to posit possible mechanisms of the MPA-mediated increase in HIV-1 acquisition.
Authors: Lyndsey R Buckner; Erma Z Drobnis; Molly S Augustine; Lynette K Rogers; Jill Akers; Patricia D Mott; Thomas J Hope; Alison J Quayle; Danny J Schust Journal: PLoS One Date: 2019-05-16 Impact factor: 3.240
Authors: Maria Röhl; Annelie Tjernlund; Julie Lajoie; Gabriella Edfeldt; Frideborg Bradley; Sofia Bergström; Vilde Kaldhusdal; Alexandra Åhlberg; Anna Månberg; Kenneth Omollo; Geneviève Boily-Larouche; Muhammad Asghar; Douglas S Kwon; Julius Oyugi; Joshua Kimani; Peter Nilsson; Keith R Fowke; Kristina Broliden Journal: Vaccines (Basel) Date: 2021-03-04