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

活性氧如何介导内分泌干扰剂对生殖器官的影响？

• 批准号: 13671718
• 负责人: SASAKI Junzo
• 金额: $ 2.62万
• 依托单位: Okayama University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671718/
• 关键词: endocrine-disrupting agents; DEHP; testis; rat; apoptosis; reactive oxygen species; DNA array; in situ hybridization; DNDアレイ; 内分泌撹乱物質; cDNAマイクロアレイ

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.

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。

项目成果

Yamamoto, H et al.: "The expression of copper, zinc superoxide dismutase(Cu/Zn-SOD) in the rat submandibular gland"Biomed Res. 23. 85-90 (2002)

Yamamoto, H 等：“大鼠颌下腺中铜、锌超氧化物歧化酶 (Cu/Zn-SOD) 的表达”Biomed Res。

Fusanori Nishimura et al.: "Cathepsin-L, a key molecule in the pathogenesis of drug-induced and I-cell disease-mediated gingival overgrowth"Am J Pathol. 161・6. 2047-2052 (2002)

Fusanori Nishimura 等：“组织蛋白酶-L，药物诱导和 I 细胞疾病介导的牙龈过度生长的发病机制中的关键分子”Am J Pathol 161·6 (2002)。

Ito, S.: "A novel WD40 repeat protein, WDC146, highly expressed during spermatogenesis in a stage-specific manner"Biochem.Biophys.Res.Commun.. 280. 656-663 (2001)

Ito, S.：“一种新型 WD40 重复蛋白 WDC146，在精子发生过程中以特定阶段的方式高度表达”Biochem.Biophys.Res.Commun. 280. 656-663 (2001)

Ito, S et al.: "A novel WD40 repeat protein, WDC146, highly expressed during spermatogenesis in a stage-specific manner"Biochem Biophys Res Commun. 280. 656-663 (2001)

Ito, S 等人：“一种新型 WD40 重复蛋白 WDC146，在精子发生过程中以特定阶段的方式高度表达”Biochem Biophys Res Commun。

Hitoshi Yamamoto et al.: "The expression of copper, zinc superoxide dismutase (Cu/Zn-SOD) in the rat submandibular gland"Biomedical Research. 23・2. 85-90 (2002)

Hitoshi Yamamoto 等：“大鼠颌下腺中铜、锌超氧化物歧化酶（Cu/Zn-SOD）的表达”生物医学研究 85-90（2002）。