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Peer-reviewedCC BYInternational Journal of Molecular Sciences

The Role of Immunologic Factors in Endometrial Receptivity: An Embryo–Endometrium Dialogue

  • Evangelia Panagodimou1
  • Ianthi Terzopoulou2
  • Olga Triantafyllidou3
  • Georgios Κ. Markantes2
  • Neoklis A. Georgopoulos2
  • Nikolaos Vlahos3
  • George L. Adonakis2
  • Apostolos I. Kaponis2
  1. 1Dept. of Obstetrics & Gynecology , IASO Clinic , 151 23 Maroussi , Athens
  2. 2Dept. Of Obstetrics & Gynecology , Aretaieio Hospital , Medical School of Athens , 115 28 , Athens
  3. 3Dept. Of Obstetrics & Gynecology , Medical School of Patras , 26 221 Rio Patron
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Abstract

Successful embryo implantation requires dynamic, bidirectional communication between a developmentally competent blastocyst and a receptive endometrium, integrating hormonal, molecular, and immunologic signals. Increasing evidence indicates that endometrial receptivity is critically dependent on a specialized immune microenvironment that supports trophoblast invasion while maintaining maternal tolerance. This review synthesizes current knowledge on the immunologic regulation of implantation, with emphasis on uterine natural killer (uNK) cells, regulatory T cells (Tregs), macrophages, dendritic cells, and cytokine networks. We further examine intracellular signaling pathways-including JAK/STAT, PI3K/AKT, NF-κB, and MAPK-that integrate immune and decidual responses. The bidirectional embryo-endometrium dialogue is explored through embryo-derived mediators such as human chorionic gonadotropin (hCG), cytokines, growth factors, and extracellular vesicles. The endometrium is increasingly recognized as a biosensor of embryo quality, selectively supporting viable embryos. Disruption of this complex communication network is implicated in recurrent implantation failure and early pregnancy loss. Despite substantial mechanistic advances, clinical translation remains limited. Emerging strategies, including immune profiling, microbiome modulation, and extracellular vesicle-based diagnostics, hold promise for precision reproductive medicine.

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Cite

BibTeXRIS
BibTeX
@article{panagodimou2026role,
  title = {{The Role of Immunologic Factors in Endometrial Receptivity: An Embryo–Endometrium Dialogue}},
  author = {Evangelia Panagodimou and Ianthi Terzopoulou and Olga Triantafyllidou and Georgios Κ. Markantes and Neoklis A. Georgopoulos and Nikolaos Vlahos and George L. Adonakis and Apostolos I. Kaponis},
  journal = {International Journal of Molecular Sciences},
  year = {2026},
  month = may,
  doi = {10.3390/ijms27104588},
  url = {https://doi.org/10.3390/ijms27104588},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - The Role of Immunologic Factors in Endometrial Receptivity: An Embryo–Endometrium Dialogue
AU  - Evangelia Panagodimou
AU  - Ianthi Terzopoulou
AU  - Olga Triantafyllidou
AU  - Georgios Κ. Markantes
AU  - Neoklis A. Georgopoulos
AU  - Nikolaos Vlahos
AU  - George L. Adonakis
AU  - Apostolos I. Kaponis
PY  - 2026
DA  - 2026/05/20
JO  - International Journal of Molecular Sciences
DO  - 10.3390/ijms27104588
UR  - https://doi.org/10.3390/ijms27104588
AB  - Successful embryo implantation requires dynamic, bidirectional communication between a developmentally competent blastocyst and a receptive endometrium, integrating hormonal, molecular, and immunologic signals. Increasing evidence indicates that endometrial receptivity is critically dependent on a specialized immune microenvironment that supports trophoblast invasion while maintaining maternal tolerance. This review synthesizes current knowledge on the immunologic regulation of implantation, with emphasis on uterine natural killer (uNK) cells, regulatory T cells (Tregs), macrophages, dendritic cells, and cytokine networks. We further examine intracellular signaling pathways-including JAK/STAT, PI3K/AKT, NF-κB, and MAPK-that integrate immune and decidual responses. The bidirectional embryo-endometrium dialogue is explored through embryo-derived mediators such as human chorionic gonadotropin (hCG), cytokines, growth factors, and extracellular vesicles. The endometrium is increasingly recognized as a biosensor of embryo quality, selectively supporting viable embryos. Disruption of this complex communication network is implicated in recurrent implantation failure and early pregnancy loss. Despite substantial mechanistic advances, clinical translation remains limited. Emerging strategies, including immune profiling, microbiome modulation, and extracellular vesicle-based diagnostics, hold promise for precision reproductive medicine.
SN  - 1422-0067
SN  - 1661-6596
ER  -