Decidualization potential of endometrial mesenchymal stem cells and their role in reproductive health

Abstract The establishment of a successful pregnancy depends on proper embryo development and coordinated endometrial differentiation, particularly through the process of decidualization. Mesenchymal stem/stromal cells (MSCs), especially those derived from endometrial tissue (eMSCs) and menstrual fluid (MenSCs), have emerged as critical players in regulating decidualization, trophoblast invasion, angiogenesis, and immune modulation at the maternal–fetal interface. These cells exhibit potent immunoregulatory functions, underscoring their role in establishing a tolerant yet responsive environment for implantation along with promoting angiogenesis and stromal regeneration. Dysfunctional MSCs have been linked to impaired decidualization and pregnancy disorders, including preeclampsia (PE) and fetal growth restriction. Evidence indicates that MenSCs from women with a history of PE exhibit diminished angiogenic potential, impaired trophoblast invasion support, and altered cytokine secretion, associating these alterations to disease pathogenesis. Similarly, aberrant eMSCs contribute to endometriosis by supporting ectopic implantation, impaired decidualization, and enhanced migration. Collectively, these findings highlight the central role of endometrial- and menstrual-derived MSCs in both reproductive success and pathology. They also emphasize their potential as diagnostic biomarkers and therapeutic targets in obstetrics and gynecology. In this review, we summarize current knowledge on the role of endometrial- and menstrual-derived MSCs in pregnancy establishment and related complications, and discuss their emerging promise as diagnostic tools and therapeutic strategies in reproductive medicine. Similar content being viewed by others Funding This work was supported by National Agency for Research and Development (ANID) through “Fondo Nacional de Desarrollo Científico y Tecnologico” [FONDECYT 1241103 (SIL) and 1230932 (LJM), FONDECYT Postdoctoral 3230201 (RP)], Subdirección de Capital Humano/Becas Doctorado Nacional/2023 21230458 (VP), and Basal Funding for Scientific and Technological Center of Excelence, IMPACT, #FB210024. Author information Authors and Affiliations Corresponding authors Ethics declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare no competing interests. Additional information Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Supplementary Information Rights and permissions Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/. About this article Cite this article Peñailillo, R., Velarde, F., Peragallo-Papic, V. et al. Decidualization potential of endometrial mesenchymal stem cells and their role in reproductive health. Reprod Biol Endocrinol (2026). https://doi.org/10.1186/s12958-026-01566-5 Received: Accepted: Published: DOI: https://doi.org/10.1186/s12958-026-01566-5