Cross-species metabolic profiling of follicular compartments in obesity

Abstract Impaired fertility in obese women is closely associated with disruptions in follicular microenvironment homeostasis. However, the underlying metabolic signatures remain poorly characterized. In this study, we employed a high-fat diet induced obese mouse model and conducted comparative metabolomic analyses of granulosa cells, follicular fluid, and serum from obese mice and women. Our results revealed prevalent metabolic disturbances across species, including dysregulated amino acid metabolism, suppressed steroidogenesis, and impaired fatty acid β-oxidation. Notably, ceramide accumulation in granulosa cells and follicular fluid suggested an insulin-resistant follicular microenvironment. These findings indicate obesity-induced metabolic reprogramming in the follicular niche, highlighting conserved disruptions in energy metabolism and steroidogenic capacity. Overall, our data provide a metabolic framework to elucidate obesity-associated subfertility and suggest potential metabolic targets for diagnosing and treating reproductive disorders.