A vaginal microbiota-ovary Axis in chemotherapy-accelerated ovarian aging: single-cell insights into cellular dysregulation

BACKGROUND: Chemotherapy-induced premature ovarian failure represents a major challenge to female reproductive health, yet the potential regulatory role of vaginal microbiota in this process remains largely unexplored. RESULTS: Using a well-established model of chemotherapy-induced ovarian aging, we observed significant disruptions in vaginal microbial ecology characterized by depletion of Lactobacillus species and concomitant enrichment of pathogenic bacteria. Microbiota transplantation effectively reversed these dysbiosis patterns and restored ovarian function. Single-cell transcriptomic analysis revealed that microbial intervention promoted the recovery of granulosa and luteal cell populations while simultaneously suppressing inflammatory activation in ovarian stromal cells, demonstrating the vaginal microbiota's capacity to maintain follicular integrity. Further mechanistic insights showed that microbiota transplantation upregulated key antioxidant defense systems and ribosomal protein networks within ovarian cells, suggesting coordinated actions to mitigate oxidative stress and enhance cellular repair capacity, although the specific microbial metabolites mediating these effects require further elucidation. CONCLUSIONS: Our findings establish for the first time the existence of a functional vaginal microbiota-ovary axis and delineate its critical role in protecting against chemotherapy-induced ovarian damage. This work not only advances our fundamental understanding of microbial-endocrine crosstalk but also identifies concrete microbial targets for developing innovative strategies to preserve fertility in cancer patients.