Vaginal <i>Escherichia coli</i> infection impairs ovarian homeostasis: Phenotypic characterization and mechanistic insights

Abstract Premature ovarian insufficiency (POI), a condition characterized by the loss of ovarian function before age 40, has emerged as a critical contributor to declining global fertility rates and the increasing prevalence of female infertility. Growing epidemiological evidence suggests that reproductive tract infections may represent a previously underappreciated risk factor for POI development, although the underlying mechanisms remain unclear. This study established a mouse model of chronic vaginal Escherichia coli (E. coli) infection to systematically investigate the potential impacts and underlying mechanisms of long-term vaginal E. coli infections on ovarian function, with particular focus on vaginal microbiota homeostasis and female reproductive health. Our study observed that long-term vaginal E. coli infection significantly impairs reproductive function of mice, manifesting as reduced fertility with diminished offspring production, concurrent with disrupted estrous cycle and impaired ovarian endocrine function. The infection caused significant ovarian reserve depletion, characterized by reduced primordial follicle counts accompanied by increased numbers of atretic follicles, as well as diminished follicular quality. Mechanistically, over-activation of the PI3K–mTORC signaling pathway was identified as a key driver of primordial follicle pool exhaustion, thereby accelerating ovarian reserve decline. These findings establish chronic reproductive tract infections as a modifiable risk factor for ovarian dysfunction, highlighting the importance of infection screening in fertility preservation strategies and paving the way for future research into microbiota-based interventions for maintaining ovarian health.