{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T05:36:40Z","timestamp":1792301800682,"version":"4.4.0"},"reference-count":36,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2019,1,19]],"date-time":"2019-01-19T00:00:00Z","timestamp":1547856000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003122","name":"Ferring","doi-asserted-by":"publisher","award":["FPP 2014"],"award-info":[{"award-number":["FPP 2014"]}],"id":[{"id":"10.13039\/501100003122","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["DFG HE 3544\/5-1"],"award-info":[{"award-number":["DFG HE 3544\/5-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Background: The molecular signature of endometrial receptivity still remains barely understood, especially when focused on the possible benefit of therapeutical interventions and implantation-related pathologies. Therefore, the protein composition of tissue and isolated primary cells (endometrial stromal cells, ESCs) from endometrial scratchings of ART (Assisted Reproductive Techniques) patients with repeated implantation failure (RIF) was compared to volunteers with proven fertility during the time of embryo implantation (LH + 7). Furthermore, an analysis of the endometrial tissue of fertile women infused with human chorionic gonadotropin (hCG) was conducted. Methods: Endometrial samples (n = 6 RIF, n = 10 fertile controls) were split into 3 pieces: 1\/3 each was frozen in liquid nitrogen, 1\/3 fixed in PFA and 1\/3 cultured. Protein lysates prepared from fresh frozen tissue were processed for mass spectrometric analysis. Results: Three proteins (EPPK1, BCLAF1 and PTMA) showed a statistically altered abundance in the endometrial tissue of RIF patients. Furthermore, pathways like metabolism, immune system, ferroptosis and the endoplasmic reticulum were altered in RIF patients. Remarkably, endometrial tissues of RIF patients showed a significantly higher (p-value = 9 \u00d7 10\u22128) protein intensity correlation (Pearson\u2019s correlation coefficient = 0.95) compared to fertile women (Pearson\u2019s correlation coefficient = 0.88). The in vivo infusion of hCG stimulated proteins of endocytosis, HIF1 signalling and chemokine production. Notably, patients suffering from RIF had a clinical pregnancy rate of 19% after the intrauterine infusion of hCG before embryo transfer (ET) compared to their failed previous cycles. Conclusion: Our study showed for the first time that the endometrial proteome composition of RIF patients differs from fertile controls during the window of implantation. The intrauterine infusion of hCG prior to an embryo transfer might improve the chemokine triggered embryo-endometrial dialogue and intensify the angiogenesis and immune response. From a clinical point of view, the hCG infusion prior to an embryo transfer might increase the pregnancy rate of RIF patients.<\/jats:p>","DOI":"10.3390\/ijms20020425","type":"journal-article","created":{"date-parts":[[2019,1,22]],"date-time":"2019-01-22T03:08:22Z","timestamp":1548126502000},"page":"425","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["A Proteome Approach Reveals Differences between Fertile Women and Patients with Repeated Implantation Failure on Endometrial Level\u2014Does hCG Render the Endometrium of RIF Patients?"],"prefix":"10.3390","volume":"20","author":[{"given":"Alexandra P.","family":"Bielfeld","sequence":"first","affiliation":[{"name":"Department of OB\/GYN and REI (UniKiD), Medical Center University of D\u00fcsseldorf, Moorenstrasse 5, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah Jean","family":"Pour","sequence":"additional","affiliation":[{"name":"Department of OB\/GYN and REI (UniKiD), Medical Center University of D\u00fcsseldorf, Moorenstrasse 5, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gereon","family":"Poschmann","sequence":"additional","affiliation":[{"name":"Molecular Proteomics Laboratory, Biomedical Research Centre (BMFZ), Heinrich-Heine-University, Universit\u00e4tsstrasse 1, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"St\u00fchler","sequence":"additional","affiliation":[{"name":"Molecular Proteomics Laboratory, Biomedical Research Centre (BMFZ), Heinrich-Heine-University, Universit\u00e4tsstrasse 1, 40225 D\u00fcsseldorf, Germany"},{"name":"Institute for Molecular Medicine, University Hospital D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6862-2143","authenticated-orcid":false,"given":"Jan-Steffen","family":"Kr\u00fcssel","sequence":"additional","affiliation":[{"name":"Department of OB\/GYN and REI (UniKiD), Medical Center University of D\u00fcsseldorf, Moorenstrasse 5, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4934-1351","authenticated-orcid":false,"given":"Dunja M.","family":"Baston-B\u00fcst","sequence":"additional","affiliation":[{"name":"Department of OB\/GYN and REI (UniKiD), Medical Center University of D\u00fcsseldorf, Moorenstrasse 5, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,1,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S19","DOI":"10.1016\/j.jrhm.2016.11.006","article-title":"Gene profiling the window of implantation: Microarray analyses from human and rodent models","volume":"2","author":"Herington","year":"2016","journal-title":"J. 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