The rodent vaginal microbiome across the estrous cycle and the effect of genital nerve electrical stimulation

Abstract

Treatment options are limited for the approximately 40% of postmenopausal women worldwide who suffer from female sexual dysfunction (FSD). Neural stimulation has shown potential as a treatment for genital arousal FSD, however the mechanisms for its improvement are unknown. One potential cause of some cases of genital arousal FSD are changes to the composition of the vaginal microbiome, which is associated with vulvovaginal atrophy. The primary hypothesis of this study was that neural stimulation may induce healthy changes in the vaginal microbiome, thereby improving genital arousal FSD symptoms. This study also sought to examine the composition of the rat vaginal microbiome, which is understudied. Nulliparous female rats were used. Treatment animals (n=5) received 30 minutes of cutaneous electrical stimulation targeting the genital branch of the pudendal nerve, and Control animals (n=4) had 30-minute sessions without stimulation. Vaginal lavage samples were taken during a 14-day baseline period including multiple estrous periods and after twice-weekly 30-minute sessions across a six-week trial period. Samples were sequenced at the University of Michigan Host Microbiome Initiative and analyzed for baseline bacterial trends and for changes due to stimulation. We found that the rat vaginal microbiome is dominated by Proteobacteria, Firmicutes, and Actinobacteria phyla bacteria, which changed in abundance during the estrous cycle and in relationship to each other. While the overall stimulation effects were unclear, some Treatment animals had lower variance in the microbiome diversity for sequential samples than Control animals, suggesting that stimulation may help normalize the vaginal microbiome. Future studies may consider additional physiological parameters, in addition to the microbiome composition, to further examine vaginal health and the effects of stimulation.

Tibial nerve stimulation increases vaginal blood perfusion and bone mineral density and yield load in ovariectomized rat menopause model

“…4) Stimulation was unilateral (compared to bilateral). The parameters selected in this study were consistent with previous nerve stimulation studies (tibial [9] or pudendal [22, 30] nerves) in rats and PTNS in humans [10]. It is possible that changing stimulation frequency could affect output, as demonstrated by the frequency-dependent effects of PTNS on the bladder (6-20 Hz is inhibitory, while 2 Hz is excitatory) [31].…”

“…Ketamine-xylazine anesthesia has also resulted in delayed recovery and possible hypoxia [36]. Animal death secondary to anesthesia decreased the sample size and strength of this study and may have contributed to variability in group measures, although previous studies [26] had as little as 5 animals per experimental group. In this study, many comparisons between OVX stim and control groups were close to significance (p = 0.05 – 0.1), and more definitive conclusions may have been drawn without animal loss decreasing sample size.…”