Objective
Premature ovarian insufficiency (POI) is a condition characterized by ovarian dysfunction occurring before the age of 40, with a prevalence ranging from 1–4%. The increasing incidence of this disease has a significant impact on women's reproductive health, as well as their metabolic, skeletal, neurological, and cardiovascular systems. The causes of premature ovarian insufficiency are multifactorial, including genetic, immunological, infectious, environmental, and iatrogenic factors, with over half of the cases remaining unexplained. Whether the microbial communities and metabolites in follicular fluid, which is the direct microenvironment for oocyte survival, are related to POI has not been reported.
Methods
This study included 26 patients with premature ovarian insufficiency and 27 controls with a normal ovarian reserve who underwent in vitro fertilization/embryo transfer. Follicular fluid samples were collected and analyzed using 16S rDNA sequencing and nontargeted metabolomics. Correlations between microbial communities and the metabolic profile of follicular fluid were analyzed to identify key microbial communities and metabolites that might be involved in the development and progression of POI.
Results
Patients with POI exhibited significant alterations in microbial richness and diversity and metabolic profiles in their follicular fluid. The downregulation of ABC transporters and upregulation of the citrate cycle (TCA cycle) might be critical for the development and progression of POI. G-Rhodopseudomonas and g-Caulobacter were identified as key microbial genera, while L-aspartic acid, citrate, isoleucine, and cytidine were identified as key metabolites.
Conclusion
This study revealed a distinctive microbial community metabolic profile in the follicular fluid of patients with POI. These findings offer novel insights into the pathogenesis of POI and might pave the way for improved clinical outcomes for individuals suffering from this condition.