Pantothenic acid alleviates endometrial injury induced by vagotomy in mice

Endometrial injury triggers inflammation responses, and persistent inflammation is a recognized cause of infertility. Emerging evidence underscores the critical role of the vagus nerve in modulating immunity. Although vagotomy is known to induce systemic inflammation, the specific mechanism by which the vagus nerve regulates uterine health is still unclear. In this study, we employed a vagotomy model to investigate the therapeutic potential of pantothenic acid in alleviating endometrial injury. Our results showed that left cervical vagotomy reduces the integrity of the endometrium and the expression of barrier proteins such as Claudin-3, Occludin, and ZO-1. Vagotomy increases the levels of inflammatory cytokines (TNF-α and IL-1β) and LPS in uterine tissue and serum through the NF-κB signaling pathway. Furthermore, we found that vagotomy promotes ferroptosis by decreasing the protein expression of SLC7A11 and GPX4 and increasing the level of COX2. Vagotomy significantly altered thecompositionof the uterine microbiota,characterized by a significant enrichment of Rodentibacter and a depletion of Vagococcus and Acetobacter. Next, we found that vagotomy can cause an increase in serum levels of lysoPE 20:4, antipyrine, and lysoPE18:2, as well as a decrease in levels of hexanoyl-L-Carnitine and pantothenic acid. When pantothenic acid was supplemented, the endometrial injury caused by vagotomy was reversed. Pantothenic acid increased the expression of barrier proteins in the endometrium and reduced the content of inflammatory cytokines in uterine tissue and serum of mice. At the same time, pantothenic acid also reversed the degree of ferroptosis induced by vagotomy in uterine tissue and serum. Our study demonstrates that vagotomy disrupts the endometrial microbiota and promotes endometrium injury and the markers of ferroptosis via the NF-κB pathway. Pantothenic acid supplementation alleviates vagus nerve-mediated endometrial injury. These results highlight that vagus nerve regulation of uterine health through pantothenic acid is a promising strategy.