Identification of novel candidate indicators for assessing zinc status during pregnancy in mice from microarray data

Wan Xu,Hongyan Wu,Lixin Shang

doi:10.1186/s40360-019-0288-8

Abstract

BackgroundThis study aimed to identify potential zinc status indicators and to clarify the mechanisms underlying zinc deficiency-induced organ damage and mortality in mice.MethodsThe dataset GSE97112, including placental tissues of mice fed diets containing normal and low concentrations of zinc, was downloaded and preprocessed. Differentially expressed genes (DEGs) were calculated and identified for zinc deficiency-related gene clusters by using the weighed gene co-expression network analysis (WGCNA) algorithm. The Gene Ontology (GO)-Biological Process (BP) and KEGG pathway of genes in the zinc deficiency-related WGCNA modules were analyzed, and the protein-protein interaction (PPI) network was constructed. In addition, modules of the PPI network were identified, and transcription factors (TFs) and miRNAs regulating DEGs were predicted. Finally, drug-gene interactions were selected.ResultsA total of 1055 DEGs containing 586 up- and 469 down-regulated genes were obtained. Three modules based on WGCNA had high correlation with degree of zinc deficiency. Annexin A1 (ANXA1), C-C motif chemokine receptor 3 (CCR3), C-X-C motif chemokine receptor 2 (CXCR2), and interleukin 2 (IL-2) were hub nodes in the PPI network. Three modules in the PPI network were identified, including module 1 associated with olfactory conduction and module 2 associated with inflammatory response. ANXA1, CCR3, and IL-2 were regulated by TFs. In addition, CXCR2, ANXA, and IL-2 were drug targets.ConclusionCXCR2, ANXA1, and CCR3 as well as olfactory receptor-related genes (proteins) may be used as biomarkers to assess zinc status in mice.

Highlights

This study aimed to identify potential zinc status indicators and to clarify the mechanisms underlying zinc deficiency-induced organ damage and mortality in mice
Previous studies have shown that changes in expression of several zinc transporters (ZnTs) influence zinc homeostasis and metabolism and subsequently change zinc status [11,12,13,14]
The distribution of gene expression levels before and after standardization showed that the gene expression levels between samples were nearly a straight line after normalization, which was suitable for further analysis

Summary

Introduction

This study aimed to identify potential zinc status indicators and to clarify the mechanisms underlying zinc deficiency-induced organ damage and mortality in mice. Zinc is an indispensable trace element during pregnancy, and zinc deficiency because of maternal nutritional deficiency can result in severe fetal growth restriction [2]. Severe zinc deficiency in pregnancy can result in increased fetal loss and high rates of congenital malformations in several. Decrease of serum zinc concentration is only detectable after long-term or severe depletion, making serum zinc an unreliable biomarker of zinc status [6]. Novel zinc biomarkers, such as the erythrocyte linoleic acid:dihomo-γ-linolenic acid ratio, negatively correlate with plasma Zn status [8,9,10]. Previous studies have shown that changes in expression of several zinc transporters (ZnTs) influence zinc homeostasis and metabolism and subsequently change zinc status [11,12,13,14]

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