ZnSO4 Protects against premature ovarian failure through PI3K/AKT/GSK3β signaling pathway.

Zinc (Zn) is an essential trace element with anti-inflammatory and antioxidant effects and plays a crucial role in the female reproductive system. We aimed to investigate the protective effect of ZnSO 4 on premature ovarian failure (POF) in SD rats and granulosa cells (GCs) treated with cisplatin. We also explored the underlying mechanisms. In vivo experiments showed that ZnSO 4 increased the serum levels of Zn2+, increased estrogen (E 2) secretion, and decreased follicle-stimulating hormone (FSH) secretion in rats. ZnSO 4 increased ovarian index, protected ovarian tissues and blood vessels, reduced excessive follicular atresia, and maintained follicular development. At the same time, ZnSO 4 inhibited apoptosis in the ovaries. In vitro experiments showed that ZnSO 4 combination treatment restored the intracellular levels of Zn2+ and inhibited the apoptosis of GCs. ZnSO 4 inhibited cisplatin-induced reactive oxygen species (ROS) production and preserved mitochondrial membrane potential (MMP). We also found that ZnSO 4 protected against POF by activating the PI3K/AKT/GSK3β signaling pathway and reducing apoptosis of GCs. These data suggest that ZnSO 4 may be a potential therapeutic agent for protecting the ovaries and preserving fertility during chemotherapy. • Our in vitro and in vivo studies confirm that cisplatin damage disrupts zinc homeostasis in vivo and granulosa cells, induces apoptosis of ovarian granulosa cells, and impairs ovarian structure and function. • ZnSO 4 treatment can increase estrogen secretion and decrease follicle-stimulating hormone secretion; it can protect the tissue interstitium and blood vessels from damage, reduce excessive follicular atresia, maintain follicular development, and play a protective role in the structure and function of prematurely failing ovaries. • ZnSO 4 treatment can inhibit cisplatin-induced reactive oxygen species production and reduction of mitochondrial membrane potential in GCs. • ZnSO 4 treatment can reduce the apoptosis of granulosa cells by activating the PI3K/AKT/GSK3β signaling pathway and play a protective role in POF. ZnSO 4 may be a potential therapeutic approach to protect ovaries and maintain fertility during chemotherapy in female cancer patients. [ABSTRACT FROM AUTHOR]