Exogenous sex steroids regulate genital epithelial barrier function in female rhesus macaques

Nirk E. Quispe Calla, Rodolfo D. Vicetti Miguel, Linda Fritts, Christopher J. Miller, Kristen M. Aceves, Thomas L. Cherpes

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

There is concern that using depot-medroxyprogesterone acetate (DMPA) for pregnancy prevention heightens HIV susceptibility. While no clinical data establishes causal link between HIV acquisition and use of this injectable progestin, prior work from our laboratory showed that DMPA comparably lowers genital levels of the cell-cell adhesion molecule desmoglein-1 (DSG1) and weakens genital epithelial barrier function in female mice and women. We likewise saw DMPA increase mouse susceptibility to multiple genital pathogens including HIV. Herein, we sought to confirm and extend these findings by comparing genital epithelial barrier function in untreated rhesus macaques (RM) vs. RM treated with DMPA or DMPA and estrogen (E). Compared to controls, genital tissue from RM with pharmacologically relevant serum levels of medroxyprogesterone acetate displayed significantly lower DSG1 levels and greater permeability to low molecular mass molecules. Conversely, DMPA-mediated effects on genital epithelial integrity and function were obviated in RM administered DMPA and E. These data corroborate the diminished genital epithelial barrier function observed in women initiating DMPA and identify RM as a useful preclinical model for defining effects of exogenous sex steroids on genital pathogen susceptibility. As treatment with E averted DMPA-mediated loss of genital epithelial barrier function, our results also imply that contraceptives releasing progestin and E may be less likely to promote transmission of HIV and other sexually transmitted pathogens than progestin-only compounds.

Original languageEnglish (US)
Pages (from-to)310-317
Number of pages8
JournalBiology of reproduction
Volume103
Issue number2
DOIs
StatePublished - Aug 1 2020

Keywords

  • Estrogen
  • Genital epithelial barrier function
  • Nonhuman primate
  • Progestin

ASJC Scopus subject areas

  • Reproductive Medicine
  • Cell Biology

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