Presence of fetal microchimerisms in the heart and effect on cardiac repair

Front Cell Dev Biol. 2024 Aug 5:12:1390533. doi: 10.3389/fcell.2024.1390533. eCollection 2024.

Abstract

Multiple complex biological processes take place during pregnancy, including the migration of fetal cells to maternal circulation and their subsequent engraftment in maternal tissues, where they form microchimerisms. Fetal microchimerisms have been identified in several tissues; nevertheless, their functional role remains largely unknown. Different reports suggest these cells contribute to tissue repair and modulate the immune response, but they have also been associated with pre-eclampsia and tumor formation. In the maternal heart, cells of fetal origin can contribute to different cell lineages after myocardial infarction. However, the functional role of these cells and their effect on cardiac function and repair are unknown. In this work, we found that microchimerisms of fetal origin are present in the maternal circulation and graft in the heart. To determine their functional role, WT female mice were crossed with male mice expressing the diphtheria toxin (DT) receptor. Mothers were treated with DT to eliminate microchimerisms and the response to myocardial infarction was investigated. We found that removal of microchimerisms improved cardiac contraction in postpartum and post-infarction model females compared to untreated mice, where DT administration had no significant effects. These results suggest that microchimerisms play a detrimental role in the mother following myocardial infarction.

Keywords: animal models; chimerism; echocardiography; feto-maternal microchimerism; myocardial infarction.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This research was funded by the Ministerio de Ciencia, Innovación y Universidades, Instituto de Salud Carlos III grant PI18/00462 to MG-G, was co-financed by the European Regional Development Fund, “A way of making Europe”. Grant PLEC2022-009235 funded by MICIU /AEI /10.13039/501100011033 and by the “European Union NextGenerationEU/ PRTR. Grant PID2022-141080OB-C21 funded by MICIU/AEI /10.13039/501100011033 and by FEDER, UE. This study has been funded by Instituto de Salud Carlos III (ISCIII) through the project “DTS22/00030” and co-funded by the European Union. This work was partially supported by Comunidad de Madrid (S2017/BMD-3867 RENIM-CM) and co-financed by European Structural and Investment Fund. The CNIC is supported by the Ministerio de Ciencia, Innovación y Universidades and the Pro CNIC Foundation and is a Severo Ochoa Centre of Excellence (SEV-2015-0505). VL: grant Intramural Programme of IiSGM for the Promotion of R&D&I 2023, Sub-programme “Pre-doctoral training contract”.