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.

中文翻译：

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外源性类固醇调节雌性恒河猴的生殖器上皮屏障功能。

有人担心使用长效醋酸甲羟孕酮 (DMPA) 预防怀孕会增加 HIV 易感性。虽然没有临床数据确定 HIV 感染和使用这种可注射孕激素之间的因果关系，但我们实验室之前的工作表明，DMPA 可比较降低细胞 - 细胞粘附分子桥粒蛋白-1（DSG1）的生殖器水平并削弱女性生殖器上皮屏障功能老鼠和女人。我们同样看到 DMPA 增加了小鼠对包括 HIV 在内的多种生殖器病原体的易感性。在此，我们试图通过比较未经治疗的恒河猴 (RM) 与用 DMPA 或 DMPA 和雌激素 (E) 治疗的 RM 的生殖器上皮屏障功能来确认和扩展这些发现。与对照相比，具有药理学相关血清醋酸甲羟孕酮水平的 RM 生殖器组织显示出显着较低的 DSG1 水平和更大的低分子量分子渗透性。相反，DMPA 介导的对生殖器上皮完整性和功能的影响在 RM 施用 DMPA 和 E 中被排除。这些数据证实了在启动 DMPA 的女性中观察到的生殖器上皮屏障功能减弱，并确定 RM 是一种有用的临床前模型，用于定义外源性类固醇的作用关于生殖器病原体的易感性。由于 E 治疗避免了 DMPA 介导的生殖器上皮屏障功能丧失，我们的结果还暗示，与仅使用孕激素的化合物相比，释放孕激素和 E 的避孕药可能不太可能促进 HIV 和其他性传播病原体的传播。