DNA Methylation Profiles of Ovarian Granular Cells from Fluorosis Female Patients Suffering Reproductive Dysfunctions

Fluorosis often causes female reproductive dysfunction. A rapid turnover of DNA methylation is a pathological change in many human diseases, including female reproductive dysfunction. The role of DNA methylation in fluorosis was unknown and investigated in this experiment. Fifty fluorosis women patients were selected as High F group and forty-six healthy women were recruited as Control group were enrolled. In addition, ovarian granulosa cells were obtained from five women in High F group and five women in Control group. All ten women went through in vitro fertilization (IVF) process with DNA methylation sequencing. KGN cells (human granulosa cell line) were cultured with different concentrations of sodium fluoride (0-8 mM NaF) for 24 h for the in vitro study. The level of DNA methylation in blood samples was significantly higher in High F group than that in Control group. The level of serum estradiol (E₂) was significantly lower in women from High F group, while the levels of serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in High F group were significantly higher than that in Control group. The methylation sequences of KGN cells relating to autophagy were significantly changed by NaF treatment dose-dependently. Based on these results, it is concluded that DNA methylation and autophagy may play a significant role in the pathophysiology of reproductive dysfunction caused by fluorosis.