PR002334 (Project)

Description:Decline in ovarian function with age not only affects fertility but is also linked to a higher risk of age-related diseases in women (e.g. osteoporosis, dementia). Intriguingly, earlier menopause is linked to shorter lifespan; however, the underlying molecular mechanisms of ovarian aging are not well understood. Recent evidence suggests the gut microbiota may influence ovarian health. In this study, we characterized ovarian aging associated microbial profiles in mice and investigated the effect of the gut microbiome from young and estropausal female mice on ovarian health through fecal microbiota transplantation. We demonstrate that the ovarian transcriptome can be broadly remodeled after heterochronic microbiota transplantation, with a reduction in inflammation-related gene expression and trends consistent with transcriptional rejuvenation. Consistently, these mice exhibited enhanced ovarian health and increased fertility. We also identified candidate microbial species potentially responsible for the observed transcriptomic changes through causal mediation analyses. To investigate whether these effects are mediated through modulation of the serum metabolome, we conducted untargeted metabolomics on serum extracted from mice subject to fecal microbiota transplantation from young and estropausal female mice. We identified several metabolites which show significant differences between groups. Our findings reveal a direct link between the gut microbiota and ovarian health.