邻苯二甲酸盐
转铁蛋白受体
脂质过氧化
支持细胞
转铁蛋白
细胞外
血睾丸屏障
生物
内分泌学
细胞生物学
化学
内科学
男科
精子发生
氧化应激
医学
有机化学
作者
Yi Zhao,Hao Zhang,Jia-Gen Cui,Jiaxin Wang,Ming-Shan Chen,Haoran Wang,Xuenan Li,Jinlong Li
出处
期刊:Redox biology
[Elsevier]
日期:2023-02-01
卷期号:59: 102584-102584
被引量:34
标识
DOI:10.1016/j.redox.2022.102584
摘要
The global rate of human male infertility is rising at an alarming rate owing to environmental and lifestyle changes. Phthalates are the most hazardous chemical additives in plastics and have an apparently negative impact on the function of male reproductive system. Ferroptosis is a recently described form of iron-dependent cell death and has been linked to several diseases. Transferrin receptor (TfRC), a specific ferroptosis marker, is a universal iron importer for all cells using extracellular transferrin. We aim to investigate the potential involvement of ferroptosis during male reproductive toxicity, and provide means for drawing conclusions on the effect of ferroptosis in phthalates-induced male reproductive disease. In this study, we found that di (2-ethylhexyl) phthalate (DEHP) triggered blood-testis barrier (BTB) dysfunction in the mouse testicular tissues. DEHP also induced mitochondrial morphological changes and lipid peroxidation, which are manifestations of ferroptosis. As the primary metabolite of DEHP, mono-2-ethylhexyl phthalate (MEHP) induced ferroptosis by inhibiting glutathione defense network and increasing lipid peroxidation. TfRC knockdown blocked MEHP-induced ferroptosis by decreasing mitochondrial and intracellular levels of Fe2+. Our findings indicate that TfRC can regulate Sertoli cell ferroptosis and therefore is a novel therapeutic molecule for reproductive disorders in male patients with infertility.
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