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Biomedicines
Volume 13
Issue 11
10.3390/biomedicines13112800
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Altered Endometrial Memory T-Cell Profiles During the Window of Implantation in Women with Previous Miscarriage

by
Dimitar Parvanov
1,*,
Rumiana Ganeva
1,
Margarita Ruseva
1,
Maria Handzhiyska
1,
Jinahn Safir
1,
Lachezar Jelezarsky
1,
Dimitar Metodiev
2,
Georgi Stamenov
3 and
Savina Hadjidekova
4
1
Department of Research, Nadezhda Women’s Health Hospital, 1330 Sofia, Bulgaria
2
Department of Clinical Pathology, Nadezhda Women’s Health Hospital, 1330 Sofia, Bulgaria
3
Department of Obstetrics and Gynecology, Nadezhda Women’s Health Hospital, 1330 Sofia, Bulgaria
4
Department of Medical Genetics, Medical University of Sofia, 1431 Sofia, Bulgaria
*
Author to whom correspondence should be addressed.
Biomedicines 2025, 13(11), 2800; https://doi.org/10.3390/biomedicines13112800
Submission received: 18 October 2025 / Revised: 5 November 2025 / Accepted: 14 November 2025 / Published: 17 November 2025
(This article belongs to the Section Immunology and Immunotherapy)
Versions Notes

Abstract

Aim: This study aimed to characterize and compare the composition of central (TCM), effector (TEM), tissue-resident (TRM), and terminally differentiated (TEMRA) memory T cells in mid-luteal endometrium during the window of implantation (WOI) in women with and without a previous miscarriage. Methods: Stromal lymphocytes from endometrial samples (P + 5) were analyzed by multicolor flow cytometry to quantify total, CD4+ and CD8+ TCM (CD45RA−CCR7+), TEM (CD45RA−CCR7−), TRM (CD69+), and TEMRA (CD45RA+CCR7−) subsets. Participants were grouped as having no previous miscarriage (n = 38) or ≥1 previous miscarriage (n = 33), and the relative distribution of these memory subsets was compared between groups. Correlations, PCA and logistic regression were used to assess global memory network organization. Results: Women with prior miscarriage exhibited higher TCM proportions among total and CD8+ lymphocytes (p < 0.01), alongside lower CD8+ TEM (p = 0.02) and higher CD4+ TEM (p = 0.01). TRM showed a mild, non-significant increase (p = 0.18), while TEMRA remained stable. TRM correlated positively with both TCM (r = 0.51) and CD4+ TEM (r = 0.40), indicating coordinated organization among memory subsets. Multivariate analyses (PCA and logistic regression) confirmed these trends and identified the TCM/TEM ratio as the most discriminative parameter. Conclusions: Endometrial memory T-cell composition during the WOI differs in women with miscarriage history, characterized by central memory expansion and reduced effector memory proportions, with parallel increases in tissue-resident cells. These changes suggest persistent remodeling of the local immune memory network toward a long-lived, less differentiated phenotype that may influence implantation readiness in subsequent cycles.
Keywords: human endometrium; window of implantation; memory T cells; central memory T cells (TCM); effector memory T cells (TEM); tissue-resident memory T cells (TRM); terminally differentiated effector memory T cells (TEMRA); miscarriage; reproductive immunology human endometrium; window of implantation; memory T cells; central memory T cells (TCM); effector memory T cells (TEM); tissue-resident memory T cells (TRM); terminally differentiated effector memory T cells (TEMRA); miscarriage; reproductive immunology

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MDPI and ACS Style

Parvanov, D.; Ganeva, R.; Ruseva, M.; Handzhiyska, M.; Safir, J.; Jelezarsky, L.; Metodiev, D.; Stamenov, G.; Hadjidekova, S. Altered Endometrial Memory T-Cell Profiles During the Window of Implantation in Women with Previous Miscarriage. Biomedicines 2025, 13, 2800. https://doi.org/10.3390/biomedicines13112800

AMA Style

Parvanov D, Ganeva R, Ruseva M, Handzhiyska M, Safir J, Jelezarsky L, Metodiev D, Stamenov G, Hadjidekova S. Altered Endometrial Memory T-Cell Profiles During the Window of Implantation in Women with Previous Miscarriage. Biomedicines. 2025; 13(11):2800. https://doi.org/10.3390/biomedicines13112800

Chicago/Turabian Style

Parvanov, Dimitar, Rumiana Ganeva, Margarita Ruseva, Maria Handzhiyska, Jinahn Safir, Lachezar Jelezarsky, Dimitar Metodiev, Georgi Stamenov, and Savina Hadjidekova. 2025. "Altered Endometrial Memory T-Cell Profiles During the Window of Implantation in Women with Previous Miscarriage" Biomedicines 13, no. 11: 2800. https://doi.org/10.3390/biomedicines13112800

APA Style

Parvanov, D., Ganeva, R., Ruseva, M., Handzhiyska, M., Safir, J., Jelezarsky, L., Metodiev, D., Stamenov, G., & Hadjidekova, S. (2025). Altered Endometrial Memory T-Cell Profiles During the Window of Implantation in Women with Previous Miscarriage. Biomedicines, 13(11), 2800. https://doi.org/10.3390/biomedicines13112800

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