Complement in human pre-implantation embryos : attack and defense
Reichhardt, Martin P.; Lundin, Karolina; Lokki, A. Inkeri; Recher, Gaëlle; Vuoristo, Sanna; Katayama, Shintaro; Tapanainen, Juha S.; Kere, Juha; Meri, Seppo; Tuuri, Timo (2019-09-18)
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
© 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.
https://creativecommons.org/licenses/by/4.0/
https://urn.fi/URN:NBN:fi-fe202004019995
Tiivistelmä
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.
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