Tauroursodeoxycholic acid rescues aged oocyte maturation in vitro by alleviating ER stress-induced PERK-eIF2α-CHOP activation

This study investigated the molecular mechanisms through which tauroursodeoxycholic acid (TUDCA) improves the in vitro maturation (IVM) efficiency of aged oocytes, utilizing germinal vesicle (GV)-stage oocytes from aged (45-week-old) and young (6-week-old) mice, as well as human oocytes from women aged ≥ 38 and ≤ 30 years. Microproteomic analysis revealed that aging oocytes exhibit significantly exacerbated endoplasmic reticulum stress (ERS) during IVM, leading to reactive oxygen species accumulation and mitochondrial dysfunction. Treatment with 100 μM TUDCA attenuated ERS and consequently suppressed ERS-induced activation of the PERK-eIF2α-CHOP pathway, significantly enhancing the first polar body extrusion rate while reducing spindle abnormalities in aged oocytes. Furthermore, TUDCA improved mitochondrial function and decreased ROS accumulation in IVM-treated oocytes, thereby enhancing post-fertilization embryo developmental potential. In human oocyte IVM experiments, TUDCA likewise enhanced oocyte maturation in women of advanced maternal age and alleviated endoplasmic reticulum stress. These findings suggest that TUDCA may improve IVM outcomes in aged oocytes, potentially through modulation of key ERS pathways, and provide an experimental basis for optimizing related culture strategies in assisted reproductive technology (ART) for women of advanced maternal age (AMA).