Effects of chitooligosaccharide-zinc on the ovarian function of mice with premature ovarian failure via the SESN2/NRF2 signaling pathway

[ABSTRACT] Chitooligosaccharide-zinc (COS center dot Zn) is a powerful anti-oxidant and anti-aging scavenger, whose anti-oxidative ability immensely exceeds vitamin C. Therefore, this study was aimed to investigate the protective effects of COS center dot Zn against premature ovarian failure (POF) and potential mechanisms. Female KM adult mice were divided into the following groups: a treatment group (150 mg center dot kg-1 center dot d-1 COS center dot Zn), a treatment group (300 mg center dot kg-1 center dot d-1 COS center dot Zn), a prevention group, two control groups and two CY/BUS groups. COS center dot Zn (150, 300 mg center dot kg-1 center dot d-1) and COS center dot Zn (300 mg center dot kg-1 center dot d-1) were therapeutically and preventatively administered to POF mice in the treatment and prevention studies, respectively. All the groups were administered for 21 days. Fewer primary and secondary follicles were observed in the COS center dot Zn-treated groups (including the treatment and prevention groups) than those of the control groups. Meanwhile, the ovarian index and the levels of FSH and LH notably increased in the treatment and prevention groups compared with those in the CY/BUS group. The levels of MVH, OCT4 and PCNA in the treatment group (300 center dot kg-1 center dot d-1 COS center dot Zn) and MVH in the prevention group remarkably increased compared with those in the CY/BUS groups. Meanwhile, the levels of P53 and P16 protein were down-regulated in the treatment and prevention groups compared with those in the CY/BUS groups. Additionally, the amounts of Sestrin2 (SESN2) and SOD2 protein were obviously higher in the treatment group (150 mg center dot kg-1 center dot d-1 COS center dot Zn) than those in the CY/BUS groups. Similarly, the amounts of NRF2 and SESN2 protein were up-regulated in the prevention group. Besides, an increased GSH level was observed in the two treatment groups, compared with that in the CY/BUS groups, and the same trend was also present in the prevention group. Taken together, COS center dot Zn improves the ovarian and follicular development through regulating the SESN2/NRF2 signaling pathway. These results suggest the role of COS center dot Zn as a novel agent for the treatment and prevention of POF.