Role of oxidative stress in germ cell apoptosis induced by di(2-ethylhexyl)phthalate
Role of oxidative stress in germ cell apoptosis induced by di(2-ethylhexyl)phthalate
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DOI：
10.1042/bj20020254
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发表时间：
2002-08-01
影响因子：
4.1
通讯作者：
Inoue, M
中科院分区：
文献类型：
--
作者：
Kasahara, E;Sato, EF;Inoue, M
邻苯二甲酸酯被广泛用作合成聚合物的增塑剂。最近的研究表明，这些酯诱导睾丸萎缩，尽管其发病机制尚不清楚。本研究描述了氧化应激可能参与邻苯二甲酸二（2-乙基己基）酯（DEHP）引起大鼠睾丸萎缩的发病机制。生化和免疫组织化学分析显示，口服DEHP增加了活性氧的产生，同时降低了睾丸中谷胱甘肽和抗坏血酸的浓度，并选择性地诱导精细胞凋亡，从而引起睾丸萎缩。邻苯二甲酸一（2-乙基己基）酯（MEHP）是DEHP的水解代谢物，在生殖细胞中选择性地诱导氧化应激，而在支持细胞中没有。此外，MEHP选择性地诱导睾丸线粒体释放细胞色素c。这些结果表明，MEHP引起的氧化应激主要损伤线粒体功能，诱导细胞色素c的释放，从而诱导精母细胞凋亡，引起睾丸萎缩。
Phthalate esters have been used extensively as plasticizers of synthetic polymers. Recent studies have revealed that these esters induce atrophy of the testis, although its pathogenesis remains unknown. The present study describes the possible involvement of oxidative stress in the pathogenesis of atrophy of the rat testis induced by di(2-ethylhexyl)phthalate (DEHP). Biochemical and immunohistochemical analysis revealed that oral administration of DEHP increased the generation of reactive oxygen species, with concomitant decrease in the concentration of glutathione and ascorbic acid in the testis, and selectively induced apoptosis of spermatocytes, thereby causing atrophy of this organ. Oxidative stress was selectively induced in germ cells, but not in Sertoli cells, treated with mono(2-ethylhexyl)phthalate (MEHP), a hydrolysed metabolite of DEHP. Furthermore, MEHP selectively induced the release of cytochrome c from mitochondria of the testis. These results indicate that oxidative stress elicited by MEHP principally injured mitochondrial function and induced the release of cytochrome c, thereby inducing apoptosis of spermatocytes and causing atrophy of the testis.