Keywords
inflammation
recurrent implantation failures
How to Cite
Abstract
Study question: Is the endometrial receptivity in patients with recurrent implantation failures (RIF) conditioned by an alteration in the decidual program? What is known: Decidualization of endometrial stromal cells involves a spectrum of changes from which endometrial receptivity arose. Summary answer: Patients with RIF present alterations: in the decidualization program, in the associated inflammatory response and in the adhesion of the blastocyst. Study design: exploratory, prospective case-control type. Materials and Methods: The integrated bioinformatic analysis included information from public databases (Reactome, Gene Ontology, WikiPathways, KEGG, GEO) and used Gephi Software for the assembly of the networks. The HESC (Human endometrial stromal cells) cell line was used as an in vitro model of decidualization, and ex vivo, endometrial biopsies from women with RIF and fertile. The IFGBP1, Prolactin, NLPRP3 and ITGA8 genes were quantified by RT-qPCR; IL-1β by intracytoplasmic labeling and flow cytometry. Results: The in-silico analysis of the processes of decidualization, inflammation and genetic regulation allowed us to identify a network of genes that connect them. In decidualized HESC cells, we confirmed the increase in the inflammatory response (activation of the NLRP3 inflammasome and the production of active IL-1β). In another bioinformatic analysis we studied the differential expression of genes from arrays of patients with RIF. Validation in endometrial biopsies from patients with RIF showed significantly decreased expression of IFGBP1 and prolactin, NLRP3 and ITGA8 (integrin involved in blastocyst adhesion). Study limitations: Although the results were validated in endometrial samples, further studies are needed to elucidate whether these mechanisms operate similarly in vivo. Implications of the findings: The understanding of alterations in the decidualization program would contribute to clarify the “memory of the endometrium”, a field that has not yet been explored.
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