How reactive oxygen species mediate the effects of endocrine-disrupting agents on the reproductive organs?

在男性生殖器官中，过氧化氢等活性氧物种(ROS)被认为与精子功能有关。由于二(2-乙基己基)邻苯二甲酸酯(DEHP)(合成聚合物的增塑剂)引起的睾丸萎缩被抗坏血酸和维生素E抑制，ROS在发病机制中的可能作用已被提出。为了研究氧化应激在DEPH诱导的睾丸萎缩中的可能参与，研究了内源性抗氧化剂和基因表达的动态变化。DEHP给药6-9小时后，生精小管内出现退化的初级精细胞和多核精细胞，12小时后TUNEL阳性精母细胞增加。DEHP可增加睾丸组织中ROS的生成，降低睾丸组织中谷胱甘肽和抗坏血酸的浓度。DEHP的代谢产物MEHP可诱导睾丸线粒体细胞色素c的释放。DNA阵列分析显示，DEHP诱导的几个基因显著减少，但原位杂交组织化学没有显示出与基因图谱一致的基因产物定位模式。这些结果表明，DEHP引起的氧化应激诱导精母细胞凋亡，从而导致睾丸萎缩。

In male reproductive organs, reactive oxygen species (ROS) such as hydrogen peroxide are known to be involved in sperm function. As di (2-ethylhexyl) phthalate (DEHP) (the plasticizers of synthetic polymers)-induced atrophy of the testis was inhibited by administration of ascorbic acid and vitamin E, the possible role of ROS has been suggested in the pathogenesis.To test the possible involvement of oxidative stress in DEPH-induced atrophy, dynamic aspects of endogeneous antioxidants and gene expression in the rat testis were studied.Degenerated primary spermatocytes and multinucleated spermatids appeared in the seminiferous tubules after 6-9 hrs of DEHP administration, and TUNEL-positive spermatocytes increased after 12 hrs of administration. DEHP increased the generation of ROS with a concomitant decrease in the concentration of glutathione and ascorbic acid in the testis. MEHP, metabolite of DEHP, induced the release of cytochrome c from isolated mitochondria of the testis. DNA array analysis revealed that DEHP treatment induced marked decrease of several genes, however, in situ hybridization histochemistry did not show localization patterns of gene products coincident with the gene profile. These results indicate that oxidative stress elicited by the administration of DEHP induced apoptosis in spermatocytes, thereby causing the atrophy of the testis.