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 ZnSO4 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 ZnSO4 increased the serum levels of Zn2+, increased estrogen (E2) secretion, and decreased follicle-stimulating hormone (FSH) secretion in rats. ZnSO4 increased ovarian index, protected ovarian tissues and blood vessels, reduced excessive follicular atresia, and maintained follicular development. At the same time, ZnSO4 inhibited apoptosis in the ovaries. In vitro experiments showed that ZnSO4 combination treatment restored the intracellular levels of Zn2+ and inhibited the apoptosis of GCs. ZnSO4 inhibited cisplatin-induced reactive oxygen species (ROS) production and preserved mitochondrial membrane potential (MMP). We also found that ZnSO4 protected against POF by activating the PI3K/AKT/GSK3β signaling pathway and reducing apoptosis of GCs. These data suggest that ZnSO4 may be a potential therapeutic agent for protecting the ovaries and preserving fertility during chemotherapy.
Keywords: Apoptosis; Granulosa cells; PI3K/AKT/GSK3β; Premature ovarian failure; Reactive oxygen species; ZnSO(4).
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