Are there common mechanisms of aneuploidy-related abortion and defects in fetus?

Abstract

Background: Monosomies and trisomies, as the most common aneuploid abnormalities, are the leading causes of miscarriages and fetal defects in humans. Although there is evidence suggested that aneuploid may have some common aspects, their common mechanism still remains unclear. This studies objective was to explore the common mechanism of monosomies and trisomies, with a purpose to identify some critical biomarkers and pathway so as to early diagnosis and effective therapy.Methods: We obtained the mRNA expression profile of GSE114559 including 101 samples data from GEO database. These data include normal, every monosomic, and trisomic transcriptome. We conducted Limma analysis by using the adj. p<0.05 and |FC|>1 criteria to identify all monosomy-related, trisomy-related differentially expressed genes (DEGs), and also to found their overlapping DEGs through Venn diagram. We then performed Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses, protein-protein interaction(PPI) network analysis to find the functional, pathways and hub genes in these DEGs. We carried out weighted correlation network analysis (WGCNA) to further detect the candidate genes and pathways related to all DEGs and their overlappling DEGs. Finally, we further used qPCR to certify pathological change of specific genes. Results: We identified all monosomy-related, trisomy-related DEGs, and their overlapping DEGs which were enriched by spliceosome, thyroid hormone, infection-related genes and signalling pathways. We also found that epigenetic related pathways were significantly enriched in the DEGs of monosomies by GO, KEGG. We explode the hub gene and module in the DEGs of monosomies and the overlapping DEGs by PPI. Then, we found that spliceosome, thyroid hormone, infection-related genes and signalling pathways were enriched in all DEGs group and the overlapping DEGs group by weighted correlation network analysis (WGCNA). Finally, we certified some hub gene in the trisomy 21, 47, XYY samples from clinical patients by qPCR which were consistent with results of PPI analysis.Conclusion: Our study indicates the potential common mechanism underlining spliceosome, thyroid hormone and infection-related signalling pathways for both monosomies and trisomies, and the mechanism underling epigenetic for monosomies.