The Combination of Estradiol and N-acetylcysteine improves folliculogenesis and angiogenesis of mice ovarian autografts by reducing inflammation and oxidative stress

Abstract

Abstract Ischemia/Reperfusion injuries are important issues after ovarian transplantation. Our study examined the effects of N-acetylcysteine (NAC) and estradiol (E2) on mouse ovarian autografts. Mice (6–8 weeks) were divided into ovarian autograft as follows: Control: fresh ovarian tissue autograft; Sham: cryopreserved/warmed ovarian tissue V; NAC: cryopreserved/warmed ovarian tissue autograft with NAC treatment; E2: cryopreserved/warmed ovarian tissue autograft with E2 treatment; NAC + E2: cryopreserved/warmed ovarian tissue autografts with the treatment of NAC and E2. In all groups, grafts were harvested on days 2, 7, and 28 after transplantation to evaluate histological parameters, inflammation relative to genes expression, and oxidative status. Histological analysis showed that NAC, E2 and a combination of NAC&E2 significantly increased the primordial, preantral, and antral follicular number. When NAC was used, it significantly reduced the expression of Tnf-α and Fgf-2, while increased Il-1β, Il-6, and Vegf expression levels. The levels of Il-6, Fgf-2, and VEGF were dramatically increased in the E2- treated group. The Combination of NAC and E2 significantly increased levels of Il-1β, Il-6, Fgf-2, and Vegf. NAC and E2 alone or in combination, significantly increased total antioxidant capacity but did not affect the superoxide dismutase and glutathione peroxidase activities. In conclusion, after transplantation, NAC and E2 alone or in combination, could improve follicular development and angiogenesis as well as decline inflammation and ovarian oxidative damage.