Journal of Developmental Medicine(Electronic Version)  2020, Vol. 8 Issue (3): 213-219 DOI: 10.3969/j.issn.2095-5340.2020.03.005 |
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Effect of 5-fluorouracil on gene expression in embryonic brain tissues of mice with neural tube defects
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| Wang Xiuwei, Guan Zhen, Zhu Zhiqiang, et al
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Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing 100020, China
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Abstract
【Abstract】 Objective To investigate the gene expression alteration in the brain tissue of neural tube defects (NTDs) fetal mice of C57BL/6J induced by 5-fluorouracil (5-FU). Methods Specifific pathogen free (SPF) C57BL/6J pregnant mice were randomly divided into the experimental group and the control group. 5-FU (12.5 mg/kg), thymidine synthase inhibitor, was injected intraperitoneally into pregnant C57BL/6J mice in the experimental group on gestational day 7.5. The pregnant mice in the control group were intraperitoneally injected with equal volume of normal saline. The malformation and neural tube closure were carefully observed by stereomicroscope and hematoxylin-eosin (HE) staining on gestational day 13.5. The expression of different genes was studied by microarray and verifified by real-time quantitative polymerase chain reaction (RT-qPCR). The statistics analysis was performed with t test. Results The incidence of NTDs was 42.31% (22/52), especially exencephaly in the experimental group. There were no NTDs in the control group. The structure of telencephalon and hindbrain were abnormal in NTD mice by HE staining. The 137 genes were signifificantly difference in NTD mice compared with the control group, of which 40 genes were up-regulated and 97 genes were down-regulated. These genes were mainly involved in the biological
processes of multicellular organismal development, cell proliferation, differentiation, and the important
pathways related to brain development. Avp, Hes3 and Wnt1 genes, which were neural development related
genes, were chosen and validated by RT-qPCR to show the signifificantly abnormal expressions in NTD brain
tissues. Conclusion 5-FU might affect the expressions of the Avp, Hes3 and Wnt1 genes related to neural
development during the process of embryonic brain development, and then lead to the occurrence of NTDs.
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Received: 22 October 2019
Published: 28 July 2020
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