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Updated: Aug 12, 2026

Multiplexed Fluorescent Immunohistochemical Staining of Four Endometrial Immune Cell Types in Recurrent Miscarriage
Published on: August 4, 2021
Endometrial lymphoid tissue in the timed endometrial biopsy: morphometric and immunohistochemical aspects
L D Klentzeris1, J N Bulmer, A Warren
1Harris Birthright Research Centre for Reproductive Medicine, Jessop Hospital for Women, Nottingham, England.
Insights
Endometrial granulated lymphocytes proliferate in situ during the luteal phase, with significant increases in T lymphocytes and macrophages observed at specific time points. These findings offer insights into the dynamic changes within the endometrium.
Area of Science:
- Reproductive immunology
- Cell biology
- Endometrial physiology
Background:
- Endometrial granulated lymphocytes (EGLs) are key immune cells in the human endometrium.
- Their precise role and dynamics throughout the luteal phase require further elucidation.
Purpose of the Study:
- To establish a morphometric profile of EGLs.
- To investigate temporal changes in leukocyte subsets within the endometrium during the luteal phase.
Main Methods:
- Endometrial biopsies were collected from fertile women at 4, 7, 10, and 13 days post-luteinizing hormone (LH) surge.
- Morphometric analysis of EGLs was performed on resin sections.
- Leukocyte phenotyping utilized 11 monoclonal antibodies and image analysis.
Main Results:
- CD8+ T cells and CD68+ macrophages showed significant increases at specific luteal phase intervals.
- A distinct lymphocyte subset (CD56+, CD38+, CD2+) dramatically increased post-day 7.
- EGL nuclear morphology changed, suggesting in situ proliferation rather than peripheral migration.
Conclusions:
- EGLs appear to proliferate within the endometrium during the luteal phase.
- Significant increases in T lymphocytes, macrophages, and EGLs occur at distinct stages of the luteal phase.
Objectives:
The purpose of this study was to provide a morphometric profile of endometrial granulated lymphocytes and to investigate qualitative and quantitative differences in leukocyte subsets in precisely timed luteal phase endometrial biopsies.
Study Design:
Endometrial biopsies were obtained from 24 normal fertile women at 4, 7, 10, and 13 days after the luteinizing hormone surge. Endometrial granulated lymphocytes were assessed morphometrically in 2 microns resin sections. Eleven monoclonal antibodies were used to characterize leukocytes in frozen sections. Semiquantitation was performed with a Quantimet 970 image analyzer. Data were analyzed with one-way analysis of variance.
Results:
CD8+ (T suppressor-cytotoxic) cells increased significantly from 4 to 7 days after the luteinizing hormone surge, whereas CD68+ macrophages increased from days 10 to 13. Lymphocytes with an unusual phenotype (CD56+, CD38+, CD2+) increased dramatically after 7 days. The volume fraction of endometrium occupied by the nuclei of endometrial granulated lymphocytes did not alter, but their mean nuclear diameter and axial ratio decreased from days 7 to 13.
Conclusion:
The morphometric findings indicate in situ proliferation of endometrial granulated lymphocytes rather than migration from the peripheral circulation. T lymphocytes, macrophages, and endometrial granulated lymphocytes increase significantly between certain stages of the luteal phase.

