Effects of chitooligosaccharide-zinc on mice ovarian function in premature ovarian failure via regulating the sestrin2/nrf2 signaling pathway

Background: The chitosan oligosaccharide-zinc (COS·Zn) is also a powerful antioxidant and anti-aging scavenger, whose anti-oxidative ability immensely exceeds that of vitamin C. Therefore, this study aimed to investigate the protective effects and potential mechanism by which COS·Zn improves ovarian function and delays aging in POF. Methods: The female KM adult mice and POF mice were divided into treated and prevention groups; these were prophylactically or therapeutically administered COS·Zn (150mg/kg·d, 300mg/kg·d) for 21 days, respectively. Results: The number of antral follicles in COS·Zn-treated groups was lower in the treated and prevention groups than that in the control group, respectively. Obviously, the ovarian index, the level of FSH and LH all increased notably during the 300 mg/kg·d treated group and the prevention group compared with cy/bus groups. The expression of MVH, OCT4 and PCNA in the 300 mg/kg·d treated groups and MVH in the prevention groups were remarkably increased compared with the CY/BUS group. Meanwhile, the protein levels of P53 and P16 were markedly down-regulated in the treated groups and prevention groups compared with CY/BUS, except for the expression of P53 in the prevention groups. Furthermore, the Sestrin2 (SESN2) and SOD2 proteins were significantly higher in the 150 mg/kg·d treated group compared with the CY/BUS group, but the 300 mg/kg·d and CY/BUS group showed no significant difference in the level of SESN2. Similarly, the NRF2 and SESN2 proteins were up-regulated in the prevention groups, and the change in SOD2 was not significant. The results revealed increased GSH levels in the 150 mg/kg·d and 300 mg/kg·d treated groups compared with CY/BUS group, and the same trend was also shown in the prevention groups. 1 Conclusion: COS·Zn improves ovarian and follicular developmental defects caused by regulating the sestrin2-nrf2 signaling pathway, and these results suggest a novel product that is effective a POF prevention and treatment drug.