Exploring the Molecular Mechanism and Biomarker of Recurrent Spontaneous Abortion Based on RNA Sequencing Analysis

Recurrent spontaneous abortion (RSA) is defined as the failure of two or more consecutive clinical pregnancies before 20 weeks of gestation. It is a hot issue in contemporary obstetrics. The etiology of RSA is complicated. Exploring the molecular mechanisms of RSA will be helpful for the prevention and precise therapy at the molecular level. This study aimed to provide novel insights into the biological characteristics and related pathways of differentially expressed genes (DEGs) in RSA.

The data set GSE121950 was obtained from GEO data sets. We identified the DEGs using the affy pack-age in R programming software. Gene set enrichment analysis (GESA) and GenePattern tools were performed to examine the gene expression differences between RSA and control group. Protein-protein interaction (PPI) analysis was performed using STRING online tool (https://string-db.org/). qRT-PCR was carried out to validate the expression levels of DEGs in 16 villus tissue samples from patients with induced abortion and 16 villus tissue samples from RSA patients.

A total of 628 DEGs with adjPval < 0.05 and |logFC| > 1 were obtained, including 155 up-regulated genes and 473 down-regulated genes. Ten gene ontology (GO) terms and 10 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were screened out by comparing the genome-wide gene set expression patterns of normal and RSA tissues. Eight genes involved in RSA were identified from the hippo signaling pathway, cytokine-cytokine receptor interaction pathway, and allograft rejection pathway.

Present findings demonstrated that several cytokine regulation processes have a deep impact on RSA. A number of genes involved in the hippo signaling pathway, cytokine-cytokine receptor interaction pathway, and allograft rejection pathway may be critical mediators or participators in the pathogenesis of RSA. Although further in vivo and in vitro validations are required, our data may provide an important theoretical basis to elucidate the pathogenesis of RSA.