Class 0128, Xi'an Jiaotong University Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, People's Republic of China.
Class S0141, Xi'an Jiaotong University Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, People's Republic of China.
Biol Trace Elem Res. 2022 Aug;200(8):3529-3536. doi: 10.1007/s12011-021-02954-1. Epub 2021 Oct 22.
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 (E) 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.
氟中毒常导致女性生殖功能障碍。DNA 甲基化的快速周转是许多人类疾病的病理变化，包括女性生殖功能障碍。本实验研究了 DNA 甲基化在氟中毒中的作用。选择 50 名氟中毒女性患者作为高氟组，46 名健康女性作为对照组。此外，从高氟组的 5 名女性和对照组的 5 名女性中获取卵巢颗粒细胞。所有 10 名女性均进行体外受精（IVF）过程，进行 DNA 甲基化测序。用不同浓度的氟化钠（0-8mM NaF）培养 KGN 细胞（人颗粒细胞系）24 小时进行体外研究。高氟组血样中的 DNA 甲基化水平明显高于对照组。高氟组女性血清雌二醇（E）水平明显降低，而高氟组血清黄体生成素（LH）和卵泡刺激素（FSH）水平明显高于对照组。NaF 处理剂量依赖性地显著改变了与自噬相关的 KGN 细胞的甲基化序列。基于这些结果，可以得出结论，DNA 甲基化和自噬可能在氟中毒引起的生殖功能障碍的病理生理学中起重要作用。
