Abstract
Complications, such as fecal soiling, incontinence, and constipation, are major health issues for patients with anorectal malformations (ARMs) after surgery. Dysplasia of the caudal spinal cord is an increasingly pivotal area in the field of postoperative complications for patients with ARMs. However, the existing research has not fully defined the mechanism underlying ARMs development. The neurogenic locus notch homolog (Notch) signaling pathway comprises several highly conserved proteins that are involved in spinal cord developmental processes. In the present study, the emerging role of Notch1 in fetal lumbosacral spinal cords was investigated in a rat model of ARMs using ethylene thiourea. Immunohistochemical staining, western blot and quantitative reverse transcription real-time polymerase chain reaction were utilized to analyze spatiotemporal expression of Notch1 on embryonic days (E) 16, E17, E19, and E21. The expression levels of the neuronal marker neurofilament and recombination signal-binding protein-J protein were evaluated for temporal correlations to Notch1 expression. The results implied that Notch1 expression was reduced in lumbosacral spinal cord neurons of ARMs embryos compared to control embryos. These results showed that, in ARMs embryos decreased Notch1 expression is related to the dysplasia of the caudal spinal cord during embryogenesis, indicating that Notch signaling may participate pathogenic embryonic lumbosacral spinal development and may be associated with postoperative complications of ARMs.
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Acknowledgements
The Authors wish to acknowledge Key Laboratory of Health Ministry for Congenital Malformations located in Shengjing Hospital of China Medical University for the support during experiments.
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This research was supported by the National Natural Science Foundation of China (Grant Nos. 81800453, 81270436 and 81671503).
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Zhonghua Yang designed and carried out the experiments, analyzed the data and wrote the manuscript. Yuzuo Bai and Huimin Jia assisted with conducting the study and writing the manuscript. Weilin Wang designed the experiments and edited the manuscript.
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The research protocol for this study was approved by the Animal Ethics Committee of Shengjing Hospital, China Medical University (No. 2015PS213K).
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Yang, Z., Jia, H., Bai, Y. et al. Spatiotemporal expression of neurogenic locus notch homolog protein 1 in developing caudal spinal cord of fetuses with anorectal malformations from ETU-fed rats. J Mol Hist 51, 519–530 (2020). https://doi.org/10.1007/s10735-020-09900-w
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DOI: https://doi.org/10.1007/s10735-020-09900-w