2001 Fiscal Year Final Research Report Summary
MOLECULAR BIOLOGICAL STUDY ON PATHOGENESIS IN MURINE EMBRYOS WITH AN ORECTAL MALFORMATIONS
| Project/Area Number |
11671774
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatric surgery
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
TOKIWA Kazuaki KYOTO PREFECTURAL UNIVERSITY OF MEDICINE, ASSOCIATE PROFESSOR, 医学部, 助教授 (30163968)
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| Co-Investigator(Kenkyū-buntansha) |
IWAI Naomi KYOTO PREFECTURAL UNIVERSITY OF MEDICINE, PROFESSOR, 医学部, 教授 (90128695)
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| Project Period (FY) |
1999 – 2001
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| Keywords | ANORECTAL MALFORMATIONS / MURINE MODELE / MBRYOLOGY / CELL PROLIFERATION / MOLECULAR BIOLOGY / APOPTOSIS |
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| Research Abstract |
The pathogenesis of anorectal malformations (ARM) remains unclear, although several possible causative factors have been suggested using model animals from mutant strains, or induced by teratogenic agents. In this study, we examined the proliferation and programmed death (apoptosis) of cells forming the urogenitorectal region to clarify the mechanism of pathogenesis in murine models with ARM induced by etretinate, with special reference to molecular biology.
Pregnant mice were fed 60 mg/kg of etretinate on the ninth gestation day (E9).Embryos were obtained between E9.5 and E13, and prepared for histological study. Cell proliferation was examined using proliferative cell-specific nuclear antigen (PCNA) expression. Apoptosis was identified by detecting in situ DNA fragmentation using the TdT-mediated dUTP-digoxigenin nick end-labeling (TUNEL) method.
Over 95 % of etretinate-treated embryos had ARM including rectoprostatic urethral or rectocloacal fistula. In the histological study, ARM embryos showed defective cell proliferation in the cloacal membrane and excessive apoptosis in the dorsocaudal region on E11, which resulted in a lack of apoptosis in the anal orifice and a short tail on E12, respectively. Cells forming the urorectal septum showed the same pattern of cell proliferation and apoptosis both in ARM embryos and the controls.
These results suggest that impairments of embryonal cellular dynamics in the cloacal membrane and dorsocaudal region induce some types of ARM.
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