2002 Fiscal Year Final Research Report Summary
How reactive oxygen species mediate the effects of endocrine-disrupting agents on the reproductive organs?
| Project/Area Number |
13671718
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Obstetrics and gynecology
|
|---|
| Research Institution | Okayama University |
|---|
Principal Investigator |
SASAKI Junzo Okayama University Graduate School of Medicine and Dentistry, Department of Cytology and Histology, Professor, 大学院・医歯学総合研究科, 教授 (30093686)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KOSAKA Jun Okayama University Graduate School of Medicine and Dentistry, Department of Cytology and Histology, Associate Professor, 大学院・医歯学総合研究科, 助教授 (40243216)
YAMADA Teruo Okayama University Graduate School of Medicine and Dentistry, Department of Cytology and Histology, Assistant, 大学院・医歯学総合研究科, 助手 (00033225)
NOMURA Takako Okayama University Graduate School of Medicine and Dentistry, Department of Cytology and Histology, Assistant, 大学院・医歯学総合研究科, 助手 (20116437)
|
|---|
| Project Period (FY) |
2001 – 2002
|
| Keywords | endocrine-disrupting agents / DEHP / testis / rat / apoptosis / reactive oxygen species / DNA array / in situ hybridization |
|---|
| Research Abstract |
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.
|
