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Taking excessive sodium fluoride may cause female reproductive dysfunction, but underlying molecular mechanism is unclear. The ovarian granulosa cells are the key endocrine cells releasing reproductive hormones. The miRNAs in the granulosa cells play an important function in regulating reproduction. The aim of this study is to explore the role of miRNAs in granulosa cell apoptosis and autophagy, as well as estradiol (E2) release in response to excessive sodium fluoride. The ovarian granulosa cells (KGN cells) were treated in vitro by different concentrations of sodium fluoride (NaF) for 24 h. The level of estradiol (E2) in the incubation medium was measured by ELISA kits. The total RNA and protein were collected and purified from KGN cells. The expression of miRNAs was detected by the real-time PCR. The signal molecules involved in cell apoptosis and autophagy were detected by the real-time PCR and Western blotting. Six miRNAs in granulosa cells were significantly up- or downregulated by NaF and selected for real-time PCR analysis. The miR-378d was the most significantly upregulated one dose dependently by NaF. It was positively correlated to the extent of apoptosis but negatively correlated to the level of autophagy in KGN cells in response to NaF. In addition, miR-378d promoted E2 release in response to 1 and 2 mM NaF but reduced E2 release in response to 4 and 8 mM NaF treatments. It is concluded that expression of miR-378d in ovarian granulosa cells is negatively correlated to the autophagy and E2 release and positively correlated to cell apoptosis under the influence of NaF. [ABSTRACT FROM AUTHOR]

Excessive taking fluoride (F) causes severe damage to reproductive system through stimulation of apoptosis and oxidant stress. Selenium (Se) may promote anti-oxidant enzymes and invert cell apoptosis. The aim of this study was to investigate the effect of Se on peripheral blood mononuclear cell (PBMC) apoptosis and oxidant stress in women with fluorosis. Sixty women were divided into three groups according to serum and urine fluoride and hair Se as High F + high Se group, High F group and Control group. The activities of anti-oxidant enzymes, malondialdehyde (MDA) and Se were measured. The levels of sirtuin type 1 (SIRT1), estradiol (E 2), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were measured by enzyme-linked immune sorbent assay (ELISA) kits. The expression of protein and apoptosis rate were detected by Western blot and Flow cytometry. The levels of E 2 , anti-oxidant enzymes in High F group were significantly lower than that in Control group, while the levels of SIRT1 and MDA were significantly higher. The levels of anti-oxidant enzymes and heat shock protein 70 (HSP70) were significantly increased in High Se + high F group while the expression of caspase-3 was significantly increased in high F group. The levels of LH and FSH in serum were significantly increased in High F group and High Se + high F group. Therefore, Se alleviates apoptosis induced by F through improving the expression of HSP70 and reduces oxidative stress by regulating levels of SIRT1 and anti-oxidant enzymes, and the secretion of certain reproductive hormones. [ABSTRACT FROM AUTHOR]