University of Oulu

Reichhardt MP, Lundin K, Lokki AI, Recher G, Vuoristo S, Katayama S, Tapanainen JS, Kere J, Meri S and Tuuri T (2019) Complement in Human Pre-implantation Embryos: Attack and Defense. Front. Immunol. 10:2234. doi: 10.3389/fimmu.2019.02234

Complement in human pre-implantation embryos : attack and defense

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Author: Reichhardt, Martin P.1,2; Lundin, Karolina3; Lokki, A. Inkeri2,4;
Organizations: 1Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom
2Department of Bacteriology and Immunology, University of Helsinki, Helsinki, Finland
3Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
4Translational Immunology Research Program, Research Programs Unit, University of Helsinki, Helsinki, Finland
5Institut d'Optique Graduate School, CNRS - Université de Bordeaux, Talence, France
6Department of Biosciences and Nutrition, Karolinska Institutet, Solna, Sweden
7PEDEGO Research Unit, Department of Obstetrics and Gynecology, University of Oulu and Oulu University Hospital, Medical Research Center, Oulu, Finland
8School of Basic and Medical Biosciences, King's College London, London, United Kingdom
9Stem Cells and Metabolism Research Program, Folkhälsan Institute of Genetics, University of Helsinki, Helsinki, Finland
10Department of Biomedical Sciences, Humanitas University, Milan, Italy
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.4 MB)
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Language: English
Published: Frontiers Media, 2019
Publish Date: 2020-04-01


It is essential for early human life that mucosal immunological responses to developing embryos are tightly regulated. An imbalance of the complement system is a common feature of pregnancy complications. We hereby present the first full analysis of the expression and deposition of complement molecules in human pre-implantation embryos. Thus, far, immunological imbalance has been considered in stages of pregnancy following implantation. We here show that complement activation against developing human embryos takes place already at the pre-implantation stage. Using confocal microscopy, we observed deposition of activation products on healthy developing embryos, which highlights the need for strict complement regulation. We show that embryos express complement membrane inhibitors and bind soluble regulators. These findings show that mucosal complement targets human embryos, and indicate potential adverse pregnancy outcomes, if regulation of activation fails. In addition, single-cell RNA sequencing revealed cellular expression of complement activators. This shows that the embryonic cells themselves have the capacity to express and activate C3 and C5. The specific local embryonic expression of complement components, regulators, and deposition of activation products on the surface of embryos suggests that complement has immunoregulatory functions and furthermore may impact cellular homeostasis and differentiation at the earliest stages of life.

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Series: Frontiers in immunology
ISSN: 1664-3224
ISSN-E: 1664-3224
ISSN-L: 1664-3224
Volume: 10
Article number: 2234
DOI: 10.3389/fimmu.2019.02234
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
3123 Gynaecology and paediatrics
Funding: Funding for the project was provided by the Finnish Cultural Foundation, the Jenny and Antti Wihuri foundation, the Academy of Finland, Helsinki University Hospital Funds, Foundation ARC for cancer research (grant #20171206504), Knut and Alice Wallenberg Foundation, Swedish Research Council, Sigrid Jusélius Foundation, and Jane and Aatos Erkko Foundation. GR was a member of the CNRS ImaBio GdR.
Copyright information: © 2019 Reichhardt, Lundin, Lokki, Recher, Vuoristo, Katayama, Tapanainen, Kere, Meri and Tuuri. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.