Hyperglycemic condition disturbs the proliferation and cell death of neural progenitors in mouse embryonic spinal cord.
Spina bifida, which results from failure of fusion in the spinal region of neural tube, is among the most common birth defects associated with diabetic pregnancy. However, the mechanism underlying maternal diabetes-induced congenital malformations including spina bifida is not fully understood. It was hypothesized that hyperglycemic conditions affect the proliferation and apoptosis of neural progenitor cells in the developing spinal neural tube, leading to abnormal neurodevelopment. In the present study, biological processes such as proliferation and apoptosis were investigated in the neuroepithelial cells of the developing spinal neural tube of embryos from diabetic mice, and in embryonic spinal neural tube derived neural progenitor cell cultures exposed to high glucose in vitro. Maternal diabetes caused decreased proliferation and increased apoptosis of the neuroepithelial cells in the developing spinal cord of embryos from diabetic mouse. Decreased proliferation and increased apoptosis were also found in neural progenitor cells exposed to high glucose. In addition, high glucose-induced apoptosis in neural progenitor cells was associated with activation of caspase-3. Thus, high glucose disturbs both proliferation and cell death of neural progenitors in the developing spinal neural tube. This could provide a cellular mechanism by which maternal hyperglycemia induces spina bifida in embryos from diabetic pregnancy.
Gao
Qing
Q
Department of Histology and Embryology, School of Medicine, Shandong University, Jinan, Shandong, China.
Gao
Ying-Mao
YM
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D053148:Caspase 3 / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D048909:Diabetes Complications / Q000378:metabolism / Q000503:physiopathology*; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D005260:Female; D005947:Glucose / Q000633:toxicity; D006943:Hyperglycemia / Q000150:complications*; D051379:Mice; D009421:Nervous System Malformations / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism / Q000503:physiopathology; D013116:Spinal Cord / Q000002:abnormalities* / Q000378:metabolism; D016135:Spinal Dysraphism / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology*; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism*
D053148:Caspase 3; D005947:Glucose