Disturbed apoptosis and cell proliferation in developing neuroepithelium of lumbo-sacral neural tubes in retinoic acid-induced spina bifida aperta in rat
Abstract: 【Abstract】Objective To investigate the cell apoptosis in the 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. Method Spina bifida was induced by atRA in fetal rats. Cell apoptosisand cell proliferation were assessed using TUNEL labeling technique on both whole-mount and seriallysectioned embryos and mitotic markers (Ki67) assay, respectively. Results An excess of apoptosis in the neuroepithelium of embryos with spina bifida was found, which became more marked as embryos progress from E11 to E13 [ E11: (2.02±0.52)% vs (0.57± 0.23)%; E12: (3.56±0.33)% vs (0.93±0.14)%; E13: (3.76±0.37)% vs (1.24±0.21)%; P<0.001 ]. 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[ E11: (65.17±2.30)% vs (81.76± 2.17)%; E12: (63.97±3.03)% vs (76.98±5.14)%; E13: (56.86±2.80)%vs (73.43±1.99)%; P <0.001]. Conclusions AtRA-induced spina bifida in rat embryos shows increased apoptosis and decreased proliferation in the neuroepithelium of the lumbo-sacral neural tube in rat, which might contribute to the pathogenesis of neuronal deficits of spina bifida.