Department of Oral Immunology and Infectious Diseases, Division of Craniofacial Development and Anomalies, ULSD, University of Louisville, Louisville, KY 40202, United States.
Department of Oral Immunology and Infectious Diseases, Division of Craniofacial Development and Anomalies, ULSD, University of Louisville, Louisville, KY 40202, United States.
Reprod Toxicol. 2019 Jun;86:76-85. doi: 10.1016/j.reprotox.2019.04.001. Epub 2019 Apr 3.
Prenatal exposure to arsenic, a naturally occurring toxic element, causes neural tube defects (NTDs) and, in animal models, orofacial anomalies. Since aberrant development or migration of cranial neural crest cells (CNCCs) can also cause similar anomalies within developing embryos, we examined the effects of in utero exposure to sodium arsenate on gene expression patterns in pure populations of CNCCs, isolated by fluorescence activated cell sorting (FACS), from Cre/LoxP reporter mice. Changes in gene expression were analyzed using Affymetrix GeneChip microarrays and expression of selected genes was verified by TaqMan quantitative real-time PCR. We report, for the first time, arsenate-induced alterations in the expression of a number of novel candidate genes and canonical cascades that may contribute to the pathogenesis of orofacial defects. Ingenuity Pathway and NIH-DAVID analyses revealed cellular response pathways, biological themes, and potential upstream regulators, that may underlie altered fetal programming of arsenate exposed CNCCs.
产前暴露于砷，一种天然存在的有毒元素，会导致神经管缺陷（NTDs），并且在动物模型中还会导致口腔面部异常。由于颅神经嵴细胞（CNCCs）的异常发育或迁移也可能导致胚胎发育中的类似异常，因此我们研究了胎内暴露于砷酸钠对 Cre/LoxP 报告小鼠中通过荧光激活细胞分选（FACS）分离的纯 CNCCs 中基因表达模式的影响。使用 Affymetrix GeneChip 微阵列分析基因表达变化，并通过 TaqMan 定量实时 PCR 验证选定基因的表达。我们首次报告了砷酸盐诱导的一些新的候选基因和经典级联表达的改变，这些改变可能有助于口腔面部缺陷的发病机制。Ingenuity Pathway 和 NIH-DAVID 分析揭示了细胞反应途径、生物学主题和潜在的上游调节剂，这些可能是砷暴露的 CNCCs 改变胎儿编程的基础。
