ATP6V1G3 Acts as a Key Gene in Recurrent Spontaneous Abortion: An Integrated Bioinformatics Analysis

BACKGROUND The molecular mechanism of recurrent spontaneous abortion is unclear. It has been suggested that dysregulated genes participate in the pathogenesis of recurrent spontaneous abortion. The aim of this study was to identify the differentially expressed genes (DEGs) and pathways in recurrent spontaneous abortion. MATERIAL AND METHODS Gene expression data series of GSE22490 and GSE26787 were obtained from the GEO database to identify the differentially expressed genes between patients with recurrent miscarriage (Case group) and patients with uncomplicated pregnancies matched for gestational age (Control group). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEEG) were applied to enrich the biological functions and pathways of the identified differentially expressed genes. A protein-protein interaction (PPI) network was constructed thorough the STRING database. Thirty-one cases of recurrent spontaneous abortion (Case group) and 30 cases of artificial abortion (Control group) were included in the study. The protein expression of hub genes in the villi and decidua tissue of the 2 groups was detected by immunohistochemical assay. RESULTS Forty-six DEGs were identified with the enriched biological function mainly in the aspects of glutamate secretion and positive regulation of synapse assembly. KEGG pathway analysis indicated the dysregulated genes were only enriched in the glutamatergic synapse pathway. In the PPI network, 83 nodes and 273 edges with the average node degreed of 6.58 were enriched. The hub gene (ATP6V1G3) of the included 46 genes was identified using Cytohubba software. In the Case group, the high expression of ATP6V1G3 protein was detected in 13 (43.3%) and 10 (33.3%) for placental villus and decidual tissue, respectively. However, the high expression rate in the Control group was 23.3% and 16.7% for placental villus and decidual tissue, respectively. The ATP6V1G3 protein high expression rate was not significantly different between the Case and Control groups (P>0.05). CONCLUSIONS We found differential gene expression profiles in villous and decidual tissues between patients with recurrent miscarriage vs. those with uncomplicated pregnancies. Upregulation of the ATP6V1G3 gene may play an important role in the development of recurrent miscarriage.