Role Of Autophagy Mediated By ROS In Rat Ovarians' Apoptosis Induced By Fluoride Exposure

Objective: As a trace element widely prevalent throughout the environment,fluoride is essential for our human body whose damage on reproductive system has been received increasing attention.However,the underlying mechanism is still unknown.The aim of this study was to investigate the role of autophagy mediated by reactive oxygen species(ROS)in ovaries apoptosis induced by fluoride exposure.Methods: 40 female Sprague-Dawley(SD)rats were randomly divided into four groups and administered with sodium fluoride(NaF)at 10,50 and 100 mg/L via drinking water for 6 months.The ovarians were collected,one part of the ovarians were used for TUNEL,the others were used for protein extraction to determine the expression of autophagy related proteins.In vitro,rat's ovarian granulosa cells were cultured and treated with different concentrations of NaF(0.2 mM,0.4 mM,0.6 mM).Wortmannin or N-acetyl-L-cysteine(NAC)were given respectively for intervention.After exposure for 24 h,western blot were used to detect the expression of apoptosis and autophagy related proteins.Results: NaF treatment impaired ovaries,as evidenced by significantly typical histopathological damage in ovaries.In the 100 mg/L NaF treated group,autophagy related proteins were markedly increased.Apoptosis in NaF treated groups were enhanced as evidenced by the result of TUNEL.In vitro,the expression levels of autophagy and apoptosis related proteins in 0.6 mM NaF treated group were significantly increased.Moreover,the levels of ROS were increased with increasing concentrations of NaF.Wortmannin can decrease the expression levels of apoptosis related proteins induced by 0.6 mM NaF.NAC can decrease the expression levels of autophagy and apoptosis related proteins induced by 0.6 mM NaF.Conclusion: NaF can cause significant damage to ovaries.The autophagy induced by NaF were mediated by ROS and plays a vital role in apoptosis.