New insights into ovarian regression-related mitochondrial dysfunction in the late-laying period.

Duck egg production sharply decreases during the late-laying period, which likely stems from an ovarian mechanism. However, the molecular mechanisms underlying ovarian regression during the late-laying period remain unclear. In this study, egg-laying (LLP) and ceased-laying (CLP) ducks at 72 weeks of age were selected to explore the potential mechanism of ovarian regression. Proteomic analysis demonstrated the importance of mitochondrial function in ovarian regression. Notably, metabolomic analysis showed that CLP ducks disturbed TCA cycle, as exhibited by the lower fumarate content. The ovarian expression of protein markers for mitochondrial biogenesis (PGC-1α and TFAM) and function (SIRT1 and SIRT3) were suppressed in CLP ducks. CLP ducks had significantly increased MDA levels and reduced SOD, CAT, GSH-Px, and T-AOC activities, inducing excessive oxidative stress. Interestingly, ACSL4, a key regulator of ferroptosis, was associated with the mitochondrial envelope and membrane function during ovarian regression. CLP ducks showed significantly reduced GSH levels and increased Fe(2+) content, as well as decreased the expression of ferroptosis-related proteins (GPX4 and SLC7A11) and antioxidant-related proteins (COX2, CAT, SOD1, and SOD2). Collectively, our findings suggest that ovarian regression-mediated mitochondrial dysfunction contributes to oxidative stress-induced ferroptosis in ducks that have ceased laying.