Abstract

Background: Embryo-mother molecular crosstalk before implantation is supposed as an essential process for theestablishment of pregnancy. There is evidence that viable embryos secrete a specific peptide known asPreimplantation Factor (PIF), which potentially plays a role in the generation of a favorable maternalenvironment for the trip of the embryo in the fallopian tube until their implantation in the uterus wall. Thisstudy aimed to evaluate changes in the proteome of human fallopian tube explants before and after exposure toPIF stimulus.Methodology: Fallopian tube explant of a healthy woman was cut in nine sections. This was synchronized andstimulated with culture medium (control) and 100 nM PIF for 16 hours. Total proteins were extracted, digestedand tryptic peptides were analyzed by nHPLC coupled to TimsTOFpro platform. Protein identification wasperformed by Homo sapiens Swissprot (560,292 entries) with PEAKS_X. The network and enrichmentpathways analysis were performed with g: Profiler, REVIGO, and Cytoscape.Results: We identified 2460 proteins, where 188 proteins were differentially expressed in PIF treatment (1.5-foldchange in expression; adjusted p-value < 0.0039, MTC Benjamini-Hochberg). Gene Ontology and Biologicalpathway analysis of differentially expressed proteins revealed significant enrichment for proteins involved inextracellular matrix organization and modulation of the immune response in PIF treatment. Furthermore,immunomodulation molecule HLA-G was detected by proteomics and western blot only in PIF treatment.Conclusions: Our study provides the first approach to understand how fallopian tube response an embryo signals likePIF and demonstrated is a good model ex vivo for understanding embryo-maternal molecular crosstalk.