title: Progestin-Containing Contraceptives Alter Expression of Host Defense-Related Genes of the Endometrium and Cervix.
abstract: Epidemiological studies indicate that progestin-containing contraceptives increase susceptibility to HIV, although the underlying mechanisms involving the upper female reproductive tract are undefined. To determine the effects of depot medroxyprogesterone acetate (DMPA) and the levonorgestrel intrauterine system (LNG-IUS) on gene expression and physiology of human endometrial and cervical transformation zone (TZ), microarray analyses were performed on whole tissue biopsies. In endometrium, activated pathways included leukocyte chemotaxis, attachment, and inflammation in DMPA and LNG-IUS users, and individual genes included pattern recognition receptors, complement components, and other immune mediators. In cervical TZ, progestin treatment altered expression of tissue remodeling and viability but not immune function genes. Together, these results indicate that progestins influence expression of immune-related genes in endometrium relevant to local recruitment of HIV target cells with potential to increase susceptibility and underscore the importance of the upper reproductive tract when assessing the safety of contraceptive products.
authors: Department of OB/GYN & Reproductive Sciences, University of California, San Francisco, San Francisco, CA, USA.
authors: Gabriel A
authors: GA
authors: Goldfien
authors: Department of OB/GYN & Reproductive Sciences, University of California, San Francisco, San Francisco, CA, USA.
authors: Fatima
authors: F
authors: Barragan
authors: Department of OB/GYN & Reproductive Sciences, University of California, San Francisco, San Francisco, CA, USA.
authors: Joseph
authors: J
authors: Chen
authors: Department of OB/GYN & Reproductive Sciences, University of California, San Francisco, San Francisco, CA, USA.
authors: Margaret
authors: M
authors: Takeda
authors: Department of OB/GYN & Reproductive Sciences, University of California, San Francisco, San Francisco, CA, USA.
authors: Juan C
authors: JC
authors: Irwin
authors: Department of OB/GYN & Reproductive Sciences, University of California, San Francisco, San Francisco, CA, USA.
authors: Jean
authors: J
authors: Perry
authors: Departments of Clinical Pharmacy, Medicine, Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA.
authors: Ruth M
authors: RM
authors: Greenblatt
authors: Department of OB/GYN & Reproductive Sciences, University of California, San Francisco, San Francisco, CA, USA.
authors: Karen K
authors: KK
authors: Smith-McCune
authors: Department of OB/GYN & Reproductive Sciences, University of California, San Francisco, San Francisco, CA, USA giudice@obgyn.ucsf.edu.
authors: Linda C
authors: LC
authors: Giudice
mesh_terms: D000293:Adolescent; D000328:Adult; D002584:Cervix Uteri / Q000187:drug effects / Q000502:physiology*; D003271:Contraceptive Agents, Female / Q000008:administration & dosage*; D003430:Cross-Sectional Studies; D004717:Endometrium / Q000187:drug effects / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D016912:Levonorgestrel / Q000008:administration & dosage*; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage*; D011372:Progestins / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: D003271:Contraceptive Agents, Female; D011372:Progestins; D016912:Levonorgestrel; D017258:Medroxyprogesterone Acetate
keywords: cervix; endometrium; gene expression; host defense; progestin-based contraceptives
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