睾酮(贴片)
间质细胞
细胞毒性
脂质过氧化
自噬
生物
活性氧
程序性细胞死亡
谷胱甘肽
内科学
内分泌学
化学
氧化应激
细胞生物学
生物化学
体外
细胞凋亡
医学
激素
酶
促黄体激素
作者
Lu Lu,Cai-Yu Lian,Ying Lv,Shuhui Zhang,Long Wang,Lin Wang
标识
DOI:10.1016/j.scitotenv.2024.169927
摘要
Glyphosate (GLY), a widely used herbicide, can adversely affect the male reproductive health by inhibiting testosterone synthesis. Ferroptosis is a form of iron-dependent oxidative cell death that contributes to inhibition of testosterone secretion. However, it still remains unclear whether ferroptosis is involved in GLY-inhibited testosterone synthesis. Hereby, an in vitro model of 1 mM GLY-exposed testicular Leydig (TM3) cells was established to elucidate this issue. Data firstly showed that GLY causes cytotoxicity and testosterone synthesis inhibition via ferroptosis, while accumulation of lipid peroxides due to intracellular ferrous ion (Fe2+) overload and glutathione depletion is confirmed as a determinant of ferroptosis. Blockage of ferroptosis via chelation of Fe2+ or inhibition of lipid peroxidation can markedly mitigate GLY-induced testosterone synthesis inhibition. Also, autophagy activation is revealed in GLY-treated TM3 cells and nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy is involved in ferroptosis through the release of excess Fe2+. GLY-induced cytotoxicity and testosterone synthesis inhibition are significantly alleviated by NCOA4 knockdown, demonstrating the crucial role of NCOA4-mediated ferritinophagy in GLY-inhibited testosterone synthesis. In summary, this study provides solid evidence that NCOA4-mediated ferritinophagy promotes ferroptosis to inhibit testosterone synthesis, highlighting that targeting NCOA4 may be a potential therapeutic approach in GLY-induced male reproductive toxicity.
科研通智能强力驱动
Strongly Powered by AbleSci AI