Depo Provera downregulates the expression of genes involved in maintaining the mucosal immune barrier and protecting against Chlamydia infection in the murine female genital tract



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Depo Provera (depot medroxyprogesterone acetate, DMPA) is a standard pre-treatment in Chlamydia animal models to ensure reliable female genital tract infection. DMPA also increases infection with simian-human immunodeficiency virus, herpes simplex virus, and Mycobacterium tuberculosis in mice and non-human primates. In humans, DMPA has been associated with an increased risk of sexually-transmitted infection, prompting the World Health Organization to call for more research on how DMPA impacts mucosal immunity. Here, we report a transcriptomics analysis of how DMPA modulates the expression of genes related to the immune barrier in the murine female genital tract. C56Bl/6 female mice were treated subcutaneously with 2.5 mg DMPA at day -7 or days -10 and -3, corresponding to different protocols in the Chlamydia field. The cervix, uterus, and ovaries were excised, total RNA was extracted and applied to the NanoString PanCancer Immune Profiling and Host Response Panels, representing 1114 genes. DMPA treatment resulted in the differential expression of over 300 genes, including the significant downregulation of many genes involved in mucosal and cell-autonomous immunity (e.g. lipocalin 2, mucin 1, CCR3, STING, and caspase 8). Studies investigating the relative contributions of key genes and their relationship to Chlamydia infection are ongoing. These data support a model wherein DMPA weakens immune barrier functions to allow reliable Chlamydia infection in the murine female genital tract, and may also explain why DMPA use in humans is associated with increased sexually-transmitted infection.



immunology, Depo Provera, public health, Chlamydia, mucosal, hormone, birth control