Complement in Human Pre-implantation Embryos: Attack and Defense

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Reichhardt , M P , Lundin , K , Lokki , A I , Recher , G , Vuoristo , S , Katayama , S , Tapanainen , J S , Kere , J , Meri , S & Tuuri , T 2019 , ' Complement in Human Pre-implantation Embryos: Attack and Defense ' , Frontiers in Immunology , vol. 10 , 2234 . https://doi.org/10.3389/fimmu.2019.02234

Title: Complement in Human Pre-implantation Embryos: Attack and Defense
Author: Reichhardt, Martin P.; Lundin, Karolina; Lokki, A. Inkeri; Recher, Gaëlle; Vuoristo, Sanna; Katayama, Shintaro; Tapanainen, Juha S.; Kere, Juha; Meri, Seppo; Tuuri, Timo
Contributor: University of Helsinki, Department of Bacteriology and Immunology
University of Helsinki, HUS Gynecology and Obstetrics
University of Helsinki, Department of Bacteriology and Immunology
University of Helsinki, Department of Obstetrics and Gynecology
University of Helsinki, HUS Gynecology and Obstetrics
University of Helsinki, STEMM - Stem Cells and Metabolism Research Program
University of Helsinki, HUSLAB
University of Helsinki, HUS Gynecology and Obstetrics
Date: 2019-09-18
Language: eng
Number of pages: 12
Belongs to series: Frontiers in Immunology
ISSN: 1664-3224
URI: http://hdl.handle.net/10138/306549
Abstract: 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.
Subject: 3123 Gynaecology and paediatrics
reproductive immunology
mucosal immunology
complement
embryo
development
pre-implantation
MESENCHYMAL STEM-CELLS
REGULATORY PROTEINS
EXPRESSION
IMMUNE
RNA
ACTIVATION
TRANSCRIPTION
HOMEOSTASIS
MUCOSA
GENE
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