Identification of target genes in recurrent implantation failure women associated with maternal-fetal immune

Abstract

AbstractBackground Recurrent implantation failure (RIF) is one of the main reasons for the unsatisfactory pregnancy rate of in vitro fertilization-embryo transfer, however the underlying mechanism is still obscure. Methods An online tool (Gene Expression Omnibus 2R) was used to identify gene expression differences in RIF women and fertility controls endometrium. Publicly available databases including GeneMANIA, Predicting Associated Transcription factors from Annotated Affinities, JASPAR and Protein Analysis Through Evolutionary Relationships were accessed to perform an integrated bioinformatic analysis. RIF and fertility controls patients (n = 9, respectively) were recruited from January to June 2022 at Affiliated Hospital of Changchun University of Traditional Chinese Medicine. Levels of target genes in the downstream of predicted signal pathway were measured by qPCR. Results Twenty-one different expression genes (DEGs), C11ORF65, DAPK2, KLK3, PFKFB2, SLC17A4, SLC7A1, CDC7, CDH13, DHRS3, DZIP1, GUCY1B3, KIAA0040, KIR2DL1, MAP3K5, NFKBIZ, SESTD1, TBXAS1, TIAM1, TIMP3, TNFAIP2 and TTC39C were found co-differential expression in GSE92324 and GSE103465 series, 93.19% displayed similar co-expression characteristics. In addition, the transcription factors (TFs) associated with key DEGs were recogonized, including RSF, FOR1, C/EBPALPHA, HNF-1ALPHA, AR, DP1, E2F1 and LEF1.The TFs associated diseases were focused on chromosome breakage, female infertility, embryo loss, and thrombosis, which acted a crucial role in RIF. Biological process analysis discovered that enrichment of these TFs correlated with IL-18 signal pathway, steroid hormone mediated signal pathway, DNA transcription, reproductive process and embryonic organ development. IL-18 signal pathway associated pro-immune molecules were upregulated in endometrium of RIF women than control. Conclusion The current research identified target genes and downstream signaling pathways at the maternal-fetal interface by bioinformatics-based analyses. It may provide a clue for prognosis judgement and target therapies in RIF women.