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. 2019 Jun:86:76-85.
doi: 10.1016/j.reprotox.2019.04.001. Epub 2019 Apr 3.

Impact of prenatal arsenate exposure on gene expression in a pure population of migratory cranial neural crest cells

Partha Mukhopadhyay  1 , Ratnam S Seelan  1 , Robert M Greene  2 , M Michele Pisano  1
Affiliations

Impact of prenatal arsenate exposure on gene expression in a pure population of migratory cranial neural crest cells

Partha Mukhopadhyay et al. Reprod Toxicol. 2019 Jun.

Abstract

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.

Keywords: Arsenate; Craniofacial development; Embryo; Gene expression profiling; Microarray; Neural crest cells.

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Conflict of interest statement

Competing Interests: The authors have no competing financial interests.

Figures

Fig. 1.
Fig. 1.
EGFP-labeled neural crest cells in Wnt1-Cre/Z/EG transgenic mouse embryos. Photomicrograph of a GD-9.5, two-component Wnt1-Cre/Z/EG transgenic embryo, under darkfield (left) and epifluorescence (right) optics. The region, demarcated by the yellow line, was excised from the sodium arsenate- and saline-exposed embryos for fluorescence-activated cell sorting (FACS). FN: frontonasal region; MB: midbrain; HB: hindbrain.
Fig. 2.
Fig. 2.
Clustered image maps (heat maps) illustrating all genes (A) and the top thirty genes (B) differentially expressed between prenatal saline- and arsenate-exposed cranial neural crest cells (CNCCs). Each row of the clustered image map represents a gene, and each column represents one array for treatment type examined [saline (S) or arsenate (A)]. The color saturation represents the level of gene expression. The three columns marked ‘S’ represent clusters of genes from the three independent sets of CNCCs prenatally-exposed to saline (control), that exhibit increased (red) and decreased (blue) expression. The three columns marked ‘A’ represent clusters of the same genes from the three independent sets of CNCCs prenatally-exposed to arsenate. Clustered are those genes that were either up regulated (red) or down regulated (blue) in arsenate-exposed CNCCs when compared to their relative expression in saline exposed CNCCs. GeneSpring GX software (v 11.0, Agilent Technologies) was used for hierarchical clustering analysis to create a condition tree representing all of the differentially expressed genes based on their expression profiles. Genes demonstrating a 1.5-fold or greater difference (p <0.05) in expression are included in the map.
See this image and copyright information in PMC

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References

    1. Spiegelstein O, Gould A, Wlodarczyk B, Tsie M, Lu X, Le C, Troen A, Selhub J, Piedrahita JA, Salbaum JM, Kappen C, Melnyk S, James J, Finnell RH, Developmental consequences of in utero sodium arsenate exposure in mice with folate transport deficiencies, Toxicol Appl Pharmacol 203(1) (2005) 18–26. - PMC - PubMed
    1. Song G, Cui Y, Han ZJ, Xia HF, Ma X, Effects of choline on sodium arsenite-induced neural tube defects in chick embryos, Food Chem Toxicol 50(12) (2012) 4364–74. - PubMed
    1. Naujokas MF, Anderson B, Ahsan H, Aposhian HV, Graziano JH, Thompson C, Suk WA, The broad scope of health effects from chronic arsenic exposure: update on a worldwide public health problem, Environ Health Perspect 121(3) (2013) 295–302. - PMC - PubMed
    1. Mazumdar M, Valeri L, Rodrigues EG, Ibne Hasan MO, Hamid R, Paul L, Selhub J, Silva F, Mostofa MG, Quamruzzaman Q, Rahman M, Christiani DC, Polymorphisms in maternal folate pathway genes interact with arsenic in drinking water to influence risk of myelomeningocele, Birth Defects Res A Clin Mol Teratol 103(9) (2015) 754–62. - PMC - PubMed
    1. Mazumdar M, Does arsenic increase the risk of neural tube defects among a highly exposed population? A new case-control study in Bangladesh, Birth Defects Res 109(2) (2017) 92–98. - PMC - PubMed

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