HOXA9 and HOXA13 along with their shared gene targets act as common immune biomarkers in recurrent implantation failure and pre-eclampsia.

Malfunctions of the complex interactions between embryo and components of decidua lead to recurrent implantation failure (RIF) and pre-eclampsia (PE). Developmental process regulatory HOX proteins (HOXA4,7,10,11) have been extensively studied to chalk reproductive immunology-related diseases with lesser-known effects of HOXA9, HOXA13, and their targets therein. Hence, functional enrichment and differential expression analysis of HOXA9 and HOXA13 targets were conducted to identify immunological markers in RIF and PE. 517 common transcription factors (CTFs) of HOXA9 and A13 were retrieved and subjected to an in-depth bioinformatic analysis to determine different associated diseases. This was followed by pathway enrichment and protein-protein interaction analysis by DAVID and Cytoscape, respectively along with depicting structural characteristics and interaction dynamics. Overlapping CTFs in RIF and PE were identified from microarray datasets (GSE103465, GSE26787 for RIF and GSE43942, GSE10588 for PE) from GEO database to determine differentially expressed genes. Validation by qRT-PCR on eutopic endometrial samples (n = 5) obtained during window of implantation and placental tissues (n = 5) revealed significant upregulation of HOXA9 and HOXA13 with dysregulated expression of CTFs (PARVA, TFAP2A, and PHTF2) in RIF and PE. Our findings revealed common potential immune characteristics of RIF and PE which may enrich the study of related pathogenic mechanisms.