Bushen Tiaojing decoction ameliorates meiotic impairment to improve oocyte quality during aging through blocking the iron overload-induced p53/CDK1/ESPL1 pathway

The decline in oocyte quality is a key factor contributing to the age-related deterioration of female fertility. In women of advanced maternal age, impaired oocyte development is primarily manifested as meiotic abnormalities. An important underlying pathological mechanism is mitochondrial dysfunction, which is often associated with iron overload during aging. Previous studies have suggested that the traditional Chinese medicine formula Bushen Tiaojing Decoction (BSTJD) may improve oocyte quality; however, its specific protective effects in women of advanced maternal age and the related mechanisms remain unclear. This study aimed to investigate whether BSTJD ameliorates meiotic defects in oocytes from aged mice by inhibiting aging-related iron overload. We established both naturally aged and FeSO₄-induced iron overload mouse models, followed by BSTJD intervention. In vitro experiments, oocytes from aged mice were cultured and treated with BSTJD-containing serum or adenovirus Infection. The results indicated that BSTJD may improve oocyte quality under advanced maternal age conditions by inhibiting iron overload and enhancing mitochondrial function. BSTJD suppressed iron overload-induced Reactive Oxygen Species accumulation, thereby downregulating p53 and p21 expression, promoting CDK1 expression, and reducing ESPL1 expression. Through this regulatory mechanism, BSTJD prevented premature cleavage of chromosomal cohesin by ESPL1, thereby supporting the normal completion of meiosis in aged oocytes and reducing the occurrence of spindle abnormalities and aneuploidy. This study suggests that BSTJD may improve oocyte quality in aged mice by inhibiting iron overload and its downstream p53/CDK1/ESPL1 signaling pathway. This work provides experimental evidence for the clinical application of BSTJD and offers a potential target for intervention strategies aimed at improving oocyte quality decline in women of advanced maternal age.