Disturbed apoptosis and cell proliferation in developing neuroepithelium of lumbo-sacral neural tubes in retinoic acid-induced spina bifida aperta in rat.

Abstract

Spina bifida is a complex congenital malformation resulting from failure of fusion in the spinal neural tube during embryogenesis. However, the cellular mechanism underlying spina bifida is not fully understood. Here, we investigated cell apoptosis in whole embryos and proliferation of neural progenitor cells in the spinal neural tube during neurulation in all-trans retinoic acid (atRA)-induced spina bifida in fetal rats. Cell apoptosis was assessed by TUNEL assay on whole-mount and serially sectioned samples of rat embryos with spina bifida. Cell proliferation of lumbo-sacral neural progenitor cells was assessed by staining for the mitotic marker Ki67 and pH3. We found an excess of apoptosis in the neuroepithelium of embryos with spina bifida, which became more marked as embryos progress from E11 to E13. Conversely, there was a reduction in cell proliferation in spina bifida embryos, with a progressively greater difference from controls with stage from E11 to 13. Thus, atRA-induced spina bifida in rat shows perturbed apoptosis and proliferation of neural progenitors in the lumbo-sacral spinal cord during embryonic development, which might contribute to the pathogenesis of spina bifida.

• Authors: Xiaowei Wei, Hui Li, Jianing Miao, Fenghua Zhou, Bo Liu, Di Wu, Shujing Li, Lili Wang, Yang Fan, Weilin Wang, Zhengwei Yuan
• Journal: International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience (Int J Dev Neurosci) Vol. 30 Issue 5 Pg. 375-81 (Aug 2012) ISSN: 1873-474X [Electronic] United States
• PMID: 22504176 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 ISDN. Published by Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• Tretinoin
• Procollagen-Proline Dioxygenase

Topics

• Analysis of Variance
• Animals
• Animals, Newborn
• Antineoplastic Agents (toxicity)
• Apoptosis (drug effects, physiology)
• Cell Proliferation (drug effects)
• Disease Models, Animal
• Embryo, Mammalian
• Epithelium (pathology)
• Female
• Gene Expression Regulation, Developmental (drug effects)
• In Situ Nick-End Labeling
• Lumbosacral Region
• Male
• Neural Tube (pathology)
• Pregnancy
• Prenatal Exposure Delayed Effects (chemically induced, pathology, physiopathology)
• Procollagen-Proline Dioxygenase (metabolism)
• Rats
• Rats, Wistar
• Spina Bifida Cystica (chemically induced, pathology)
• Tretinoin (toxicity)