scholarly journals Maternal diabetes induces senescence and neural tube defects sensitive to the senomorphic Rapamycin

2020 ◽  
Author(s):  
Cheng Xu ◽  
Wei-Bin Shen ◽  
E. Albert Reece ◽  
Hidetoshi Hasuwa ◽  
Christopher Harman ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
Maternal Diabetes ◽  
Dominant Negative ◽  
Neural Tube Closure ◽  
Premature Senescence ◽  
Cell Cycle Regulators ◽  
Transgenic Expression ◽  
Mechanistic Basis

ABSTRACTNeural tube defects (NTDs) are the second most common structural birth defects. Senescence, a state of permanent cell cyle arrest, only occurs after neural tube closure. Maternal diabetes-induced NTDs, severe diabetic complications leading to infant mortality or lifelong morbidity, may be linked to premature senescence. Here we report that premature senescence occurs in the mouse neuroepithelium and disrupts neurulation, leading to NTDs in diabetic pregnancy. Premature senescence and NTDs were abolished by deleting the transcription factor Foxo3a, the miR-200c gene, the cell cycle inhibitors p21 or p27, or by transgenic expression of the dominant-negative FoxO3a mutant or by the senomorphic rapamycin. Double transgenic expression of p21 and p27 mimicked maternal diabetes in inducing premature neuroepithelium senescence and NTDs. These findings integrate transcription- and epigenome-regulated miRNAs and cell cycle regulators in premature neruoepithelium senescence, and provide a mechanistic basis for targeting premature senescence and NTDs using senomorphs.

scholarly journals Maternal diabetes induces senescence and neural tube defects sensitive to the senomorphic rapamycin

2021 ◽  
Vol 7 (27) ◽  
pp. eabf5089
Author(s):  
Cheng Xu ◽  
Wei-Bin Shen ◽  
E. Albert Reece ◽  
Hidetoshi Hasuwa ◽  
Christopher Harman ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
Maternal Diabetes ◽  
Dominant Negative ◽  
Neural Tube Closure ◽  
Premature Senescence ◽  
Cell Cycle Regulators ◽  
Transgenic Expression ◽  
Mechanistic Basis

Neural tube defects (NTDs) are the second most common structural birth defect. Senescence, a state of permanent cell cycle arrest, occurs only after neural tube closure. Maternal diabetes–induced NTDs are severe diabetic complications that lead to infant mortality or lifelong morbidity and may be linked to premature senescence. Here, we report that premature senescence occurs in the mouse neuroepithelium and disrupts neurulation, leading to NTDs in diabetic pregnancy. Premature senescence and NTDs were abolished by knockout of the transcription factor Foxo3a, the miR-200c gene, and the cell cycle inhibitors p21 and p27; transgenic expression of the dominant-negative FoxO3a mutant; or the senomorphic rapamycin. Double transgenic expression of p21 and p27 mimicked maternal diabetes in inducing premature neuroepithelium senescence and NTDs. These findings integrate transcription- and epigenome-regulated miRNAs and cell cycle regulators in premature neuroepithelium senescence and provide a mechanistic basis for targeting premature senescence and NTDs using senomorphics.

scholarly journals Lamin B1 Polymorphism Influences Morphology of the Nuclear Envelope, Cell Cycle Progression, and Risk of Neural Tube Defects in Mice

PLoS Genetics ◽  
2012 ◽  
Vol 8 (11) ◽  
pp. e1003059 ◽  
Author(s):  
Sandra C. P. De Castro ◽  
Ashraf Malhas ◽  
Kit-Yi Leung ◽  
Peter Gustavsson ◽  
David J. Vaux ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Nuclear Envelope ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
Cell Cycle Progression ◽  
Cycle Progression ◽  
Lamin B1

Neural Tube Defects: Prevention by Vitamin Supplements

PEDIATRICS ◽  
1982 ◽  
Vol 69 (4) ◽  
pp. 498-499
Author(s):  
R. W. Smithells
Keyword(s):  
Neural Tube ◽  
Neural Tube Defects ◽  
Birth Defect ◽  
Epidemiologic Study ◽  
Neural Tube Closure ◽  
Additive Effects ◽  
Vitamin Supplements ◽  
Tube Closure

Neural tube defects (NTD) have been the object of more intense epidemiologic study than any other kind of birth defect. This is in part because of their ready recognition at birth (and, in recent years, before birth) and in part because their consequences are usually catastrophic: they kill or they cripple. Regarding their cause, no single genetic or environmental agent has been identified (or is likely to be) and a multifactorial basis is assumed. If failure of neural tube closure results from the additive effects of several adverse factors, removal or correction of any one might shift the developmental balance across the threshold from NTD to normality.

Prevalence of Neural Tube Defects (NTDs) In And Around Varanasi Region: Some Observations

2021 ◽  
Author(s):  
Vaibhav Pandey ◽  
Surendra Kumar Pandey ◽  
Praveen Kumar Tiwari ◽  
Pragati Shakya ◽  
Shashank Shekhar Jha ◽  
...  
Keyword(s):  
Neural Tube ◽  
Neural Tube Defects ◽  
Birth Defect ◽  
Neural Tube Closure ◽  
The World ◽  
Typical Type ◽  
Males And Females ◽  
One Year ◽  
Congenital Disabilities ◽  
Tube Closure

Abstract Congenital anomalies are one of the primary causes of infant mortality and disability in the world. Neural Tube Defects (NTDs) are the most typical type of birth defect resulting from the failure of Neural tube closure. In this retrospective hospital-based study, the data of the children affected byneural tube defects (NTDs) were analyzed. Prevalence of Hydrocephalous, Myelomeningocele (MMC), Encephalocele, Lipo MMC, Meningocele, Spina Bifida Occulta among children with more or less than one year of age and their occurrence in males and females was studied. The frequency of occurrence of cases of neural tube defects was significantly less among all the congenital disabilities, i.e., 5% of total cases studied. The prevalence of myelomeningocele, hydrocephalous, and Encephalocele was higher than other types of NTDs. This study concludes that the prevalence of hydrocephalous and myelomeningocele in this area raises a concern to have more research of their etiology.

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