26562699

PMC4646715

Background

HIV acquisition in the female genital tract remains incompletely understood. Quantitative data on biological HIV risk factors, the influence of reproductive hormones, and infection risk are lacking. We evaluated vaginal epithelial thickness during the menstrual cycle in pigtail macaques (Macaca nemestrina). This model previously revealed increased susceptibility to vaginal infection during and following progesterone-dominated periods in the menstrual cycle.

Methods

Nucleated and non-nucleated (superficial) epithelial layers were quantitated throughout the menstrual cycle of 16 macaques. We examined the relationship with previously estimated vaginal SHIVSF162P3 acquisition time points in the cycle of 43 different animals repeatedly exposed to low virus doses.

Results

In the luteal phase (days 17 to cycle end), the mean vaginal epithelium thinned to 66% of mean follicular thickness (days 1-16; p=0.007, Mann-Whitney test). Analyzing four-day segments, the epithelium was thickest on days 9-12, and thinned to 31% thereof on days 29-32, with reductions of nucleated and non-nucleated layers to 36 and 15% of their previous thickness, respectively. The proportion of animals with estimated SHIV acquisition in each cycle segment correlated with non-nucleated layer thinning (Pearson’s r = 0.7, p<0.05, linear regression analysis), but not nucleated layer thinning (Pearson’s r = 0.6, p=0.15).

Conclusions

These data provide a detailed picture of dynamic cycle-related changes in the vaginal epithelium of pigtail macaques. Substantial thinning occurred in the superficial, non-nucleated layer, which maintains the vaginal microbiome. The findings support vaginal tissue architecture as susceptibility factor for infection and contribute to our understanding of innate resistance to SHIV infection.

CDC Public Access

AI-0681/AI/NIAID NIH HHS/United States
CC999999/Intramural CDC HHS/United States
Y01 AI000681-02/AI/NIAID NIH HHS/United States
Y1-AI-0681-02/AI/NIAID NIH HHS/United States