Medroxyprogesterone acetate-treated human, primary endometrial epithelial cells reveal unique gene expression signature linked to innate immunity and HIV-1 susceptibility

Am J Reprod Immunol. 2018 Jan;79(1). doi: 10.1111/aji.12781. Epub 2017 Nov 6.

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.

Keywords: HIV-1; endometrium; estradiol; medroxyprogesterone acetate; progesterone; transcriptome.

MeSH terms

  • Adult
  • Cells, Cultured
  • Cholesterol / biosynthesis
  • Contraceptive Agents, Female / administration & dosage*
  • Contraceptive Agents, Female / adverse effects
  • Disease Susceptibility
  • Epithelial Cells / drug effects*
  • Epithelial Cells / physiology
  • Female
  • Genitalia, Female / pathology*
  • HIV Infections / genetics
  • HIV Infections / immunology*
  • HIV-1 / physiology*
  • Humans
  • Immunity, Innate
  • Inflammation / genetics
  • Medroxyprogesterone Acetate / administration & dosage*
  • Medroxyprogesterone Acetate / adverse effects
  • Middle Aged
  • Mucous Membrane / pathology*
  • Primary Cell Culture
  • Progesterone / metabolism
  • Progestins / metabolism
  • Tissue Array Analysis
  • Transcriptome

Substances

  • Contraceptive Agents, Female
  • Progestins
  • Progesterone
  • Cholesterol
  • Medroxyprogesterone Acetate

Associated data

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