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ORIGINAL RESEARCH article
Front. Immunol.
Sec. Immunological Tolerance and Regulation
Volume 15 - 2024 |
doi: 10.3389/fimmu.2024.1440388
This article is part of the Research Topic Immunology at the feto-maternal interface View all 14 articles
In utero transfer of decidualized endometrial stromal cells increases the frequency of Tregs and normalizes abortion rate in the CBA/J x DBA/2 abortion model
Provisionally accepted- 1 Department of biology, Faculty of Basic sciences, University of Tehran, Tehran, Iran
- 2 Reproductive Immunology Research Center, Avicenna Research Institute, Tehran, Iran
- 3 Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
- 4 Reproductive Biotechnology Research Center, Avicenna Research Institute, Academic Center for Education, Culture and Research, Tehran, Alborz, Iran
- 5 Monoclonal Antibody Research Center, Avicenna Research Institute, Academic Center for Education, Culture and Research, Tehran, Alborz, Iran
Introduction: Failure to adequate decidualization leads to adverse pregnancy outcomes including pregnancy loss. Although there are plenty of reports underscoring immune dysfunction as the main cause of abortion in CBA/J females mated with DBA/2 males (CBA/J x DBA/2), little is known about the potential role of impaired endometrial decidualization. Methods: Endometrial stromal cells (ESCs) from CBA/J mice were in vitro decidualized and the proteome profile of secrotome was investigated by membrane-based array. CBA/J mice were perfused in utero with either decidualized ESCs (CxD/D), undecidualized ESCs (CxD/ND), or PBS (CxD/P) 12 days before mating with DBA/2 males. Control mice were not manipulated and were mated with male DBA/2 (CxD) or Balb/c (CxB) mice. At day 13.5 of pregnancy, reproductive parameters were measured. In vivo tracking of EdU-labeled ESCs was performed by fluorescence microscopy. Frequency of Tregs in paraaortic/renal and inguinal lymph nodes was measured by flow cytometry. Proliferation of pregnant CBA/J splenocytes in response to stimulation with either DBA/2 splenocytes was assessed by 5,6-carboxyfluorescein diacetate succinimidyl ester (CFSE) flow cytometry. Results: In CxD/D mice, the resorption rate was reduced to match that seen in the CxB group. Intrauterine perfused ESCs appeared in uterine stroma after 2 days, which remained there for at least 12 days. There was no difference in the number of implantation sites and embryo weight across all groups. The frequency of regulatory T cells (Treg) in the inguinal lymph nodes was similar across all groups, but it increased in the paraaortic/renal lymph nodes of CxD/D mice to the level found in CxB mice. No significant changes were observed in proliferation of splenocytes from pregnant CxD/D compared to those of CxD group in response to stimulation with DBA/2 spelnocytes. Decidualization of ESCs was associated with a profound alteration in ESC secretome exemplified by alteration in proteins involved in extracellular matrix (ECM) remodeling, response to inflammation, senescence and
Keywords: Abortion, CBA/J x DBA/2, decidualization, regulatory T cells, Proteome
Received: 29 May 2024; Accepted: 30 Aug 2024.
Copyright: © 2024 Zarnani, Zarnani, Maslehat-Lay, Zeinali, Vafaei, Shokri, Vanaki, Edalatkhah, Naderi, Sarvari, Attari, Jeddi-Tehrani and Zarnani. 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) or licensor 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.
* Correspondence:
Mahmood Jeddi-Tehrani, Monoclonal Antibody Research Center, Avicenna Research Institute, Academic Center for Education, Culture and Research, Tehran, Alborz, Iran
Amir-Hassan Zarnani, Reproductive Immunology Research Center, Avicenna Research Institute, Tehran, Iran
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