Premature ovarian failure (POF) is characterized by the cessation of ovarian function in women younger than 40 [1,2]. POF increases gonadotropin levels and decreases estrogen (E2) levels, manifesting as abnormal menstruation and decreased fertility. In addition to its effects on early menopause and infertility, POF increases the risk of osteoporosis, cardiovascular diseases, psychological problems, and other diseases that can severely affect the quality of life of women [3,4]. In clinical practice, chemotherapy drugs commonly cause POF in female patients [5,6]. Hormone replacement therapy is a standard treatment that can effectively relieve patients' symptoms but can also cause serious side effects. Particularly, it can increase the risk of developing other cancers [[7], [8], [9]]. Therefore, finding new methods for treating and preventing POF is essential.

Zinc (Zn) is an essential trace element that plays a critical regulatory role in cell growth, hormone release, immune response, and reproduction [10,11]. Cell differentiation, proliferation, and hormone secretion in the female reproductive system all need Zn [12,13]. Increased availability of Zn facilitates the proliferation of granulosa cells (GCs), follicle development, oocyte maturation, fertilization, and embryo development [14]. It has been found that Zn levels are significantly lower, and follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels are higher in patients with POF [15]. The occurrence of POF is associated with uncontrolled oxidative stress. Zn has strong antioxidant properties, regulating intracellular reactive oxygen species (ROS), reducing oxidative stress, and protecting DNA from damage. Moderate intake of Zn is essential to increase the antioxidant capacity of ovaries [16,17]. Recent studies have found that chitooligosaccharide-zinc is protective against oxidative damage in POF and may alleviate ovarian dysfunction [18]. It has been found that higher intracellular concentrations of Zn can inactivate the phosphorylation of glycogen synthase kinase 3β (GSK3β), inhibit the production of intracellular ROS, protect mitochondria from oxidative stress, and inhibit apoptosis [[19], [20], [21]]. GSK3β is an essential downstream molecule of PI3K/AKT pathway, which regulates mammalian oocyte growth and early follicle development [22,23]. Zn may protect against POF by regulating the PI3K/AKT/GSK3β signaling pathway. Although numerous researchers have focused on the role of Zn in POF, the relationship between Zn and POF still needs to be fully understood, and the relevant mechanisms must be urgently explored.

Therefore, in this study, cisplatin was used to induce POF in vivo and in vitro. We investigated the protective effect of ZnSO4 on POF and uncovered the underlying mechanism. This study provides a theoretical basis for preventing and treating chemotherapy-induced POF.