Record source
Europe PMC Research Library
Abstract / Description
Abstract Background Ferroptosis is recognized as a novel mechanism underlying ovarian aging. Our previous study revealed that PRDX4 in granulosa cells is a key factor in alleviating ovarian aging. This study was designed to investigate the precise mechanism through which PRDX4 alleviates ovarian aging. Methods The naturally aging mice were used as an in vivo model, and Tg-induced senescent KGN cells were used as an in vitro model. The expression of PRDX4 in KGN cells was manipulated via adenoviral vectors (Ad‑Prdx4 for overexpression and Ad‑Prdx4/siRNA for knockdown). Cellular senescence indicators, including senescence-associated proteins (P16 and P21), the SASP, and SA-β-gal activity, were evaluated. Ferroptosis indicators (GPX4, TFRC, and ACSL4), mitochondrial morphology, and ferrous iron levels were analyzed, and the levels of ROS and MDA were also measured. Results In the ovarian tissues of aging mice and Tg-induced senescent KGN cells, ferroptosis significantly increased, as evidenced by mitochondrial damage, increased iron accumulation, increased ROS/MDA/Fe²⁺ levels, downregulated GPX4 expression, and upregulated TFRC expression (p