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Article

A Proteome Approach Reveals Differences between Fertile Women and Patients with Repeated Implantation Failure on Endometrial Level—Does hCG Render the Endometrium of RIF Patients?

1
Department of OB/GYN and REI (UniKiD), Medical Center University of Düsseldorf, Moorenstrasse 5, 40225 Düsseldorf, Germany
2
Molecular Proteomics Laboratory, Biomedical Research Centre (BMFZ), Heinrich-Heine-University, Universitätsstrasse 1, 40225 Düsseldorf, Germany
3
Institute for Molecular Medicine, University Hospital Düsseldorf, 40225 Düsseldorf, Germany
*
Author to whom correspondence should be addressed.
These authors have contributed equally.
Int. J. Mol. Sci. 2019, 20(2), 425; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20020425
Received: 27 December 2018 / Revised: 16 January 2019 / Accepted: 17 January 2019 / Published: 19 January 2019
(This article belongs to the Special Issue Reproductive Immunology: Cellular and Molecular Biology)
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 × 10−8) protein intensity correlation (Pearson’s correlation coefficient = 0.95) compared to fertile women (Pearson’s 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. View Full-Text
Keywords: endometrial receptivity; human chorionic gonadotropin; embryo transfer; window of implantation endometrial receptivity; human chorionic gonadotropin; embryo transfer; window of implantation
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MDPI and ACS Style

Bielfeld, A.P.; Pour, S.J.; Poschmann, G.; Stühler, K.; Krüssel, J.-S.; Baston-Büst, D.M. A Proteome Approach Reveals Differences between Fertile Women and Patients with Repeated Implantation Failure on Endometrial Level—Does hCG Render the Endometrium of RIF Patients? Int. J. Mol. Sci. 2019, 20, 425. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20020425

AMA Style

Bielfeld AP, Pour SJ, Poschmann G, Stühler K, Krüssel J-S, Baston-Büst DM. A Proteome Approach Reveals Differences between Fertile Women and Patients with Repeated Implantation Failure on Endometrial Level—Does hCG Render the Endometrium of RIF Patients? International Journal of Molecular Sciences. 2019; 20(2):425. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20020425

Chicago/Turabian Style

Bielfeld, Alexandra P., Sarah J. Pour, Gereon Poschmann, Kai Stühler, Jan-Steffen Krüssel, and Dunja M. Baston-Büst 2019. "A Proteome Approach Reveals Differences between Fertile Women and Patients with Repeated Implantation Failure on Endometrial Level—Does hCG Render the Endometrium of RIF Patients?" International Journal of Molecular Sciences 20, no. 2: 425. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20020425

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