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

在男性生殖器官中，活性氧（ROS）如过氧化氢被认为与精子功能有关。由于抗坏血酸和维生素E可以抑制邻苯二甲酸二（2-乙基己基）（合成聚合物的增塑剂）引起的睾丸萎缩，因此有人认为ROS可能在其发病机制中起作用。为了测试氧化应激可能参与deph诱导的萎缩，研究了大鼠睾丸内源性抗氧化剂和基因表达的动态方面。DEHP给药6 ~ 9 h后，精管内出现原代精母细胞变性和多核精母细胞，给药12 h后tunel阳性精母细胞增多。DEHP增加ROS的产生，同时降低睾丸中谷胱甘肽和抗坏血酸的浓度。MEHP是DEHP的代谢物，诱导睾丸分离线粒体释放细胞色素c。DNA阵列分析显示，DEHP处理导致多个基因明显减少，但原位杂交组织化学未显示与基因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.