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Multiplexed Fluorescent Immunohistochemical Staining of Four Endometrial Immune Cell Types in Recurrent Miscarriage
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Increase in FoxP3, CD56 immune cells and decrease in glands PGRMC1 expression in the endometrium are associated with

Yulia Anatolievna Lyzikova1, Dmitry Aleksandrovich Zinovkin2, Md Zahidul Islam Pranjol3

  • 1Department of Obstetrics and Gynecology, Gomel State Medical University, Gomel, Belarus.

European Journal of Obstetrics, Gynecology, and Reproductive Biology
|January 1, 2020
PubMed
Summary

Increased uterine natural killer (uNK) cells, FoxP3+ regulatory T cells (Tregs), and decreased PGRMC1 expression are linked to recurrent miscarriage (RM). These factors may play a role in the development of RM, impacting reproductive health.

Keywords:
CD56FoxP3PGRMC1Recurrent miscarriageUterine NK cells

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Area of Science:

  • Reproductive immunology
  • Gynecologic pathology

Background:

  • Recurrent miscarriage (RM) is a complex condition with known risk factors including uterine abnormalities, chromosomal issues, and clotting disorders.
  • The role of specific immune cells and molecular markers within the endometrium in RM development requires further elucidation.

Purpose of the Study:

  • To investigate the potential involvement of endometrial FoxP3+ regulatory T cells (Tregs), CD56+ uterine natural killer (uNK) cells, and endometrial progesterone receptor membrane component 1 (PGRMC1) expression in the pathogenesis of recurrent miscarriage.

Main Methods:

  • A prospective study involving 102 patients with spontaneous abortion (SA), categorized into recurrent miscarriage (+RM) and non-recurrent miscarriage (-RM) groups.
  • Immunohistochemistry was employed to quantify FoxP3+ Tregs, CD56+ uNK cells, and PGRMC1 expression in endometrial tissues.
  • Statistical analyses included Mann-Whitney U test, Fisher's exact test, correlation analysis, and relative risk (RR) calculation, with significance set at p < 0.05.

Main Results:

  • The +RM group exhibited significantly higher endometrial infiltration of CD56+ uNK cells (p < 0.001) and FoxP3+ Tregs (p = 0.0005) compared to the -RM group.
  • A decreased expression of PGRMC1 was observed in the endometrium of the +RM group (p = 0.004).
  • Increased endometrial uNK cells and FoxP3+ Tregs, along with reduced PGRMC1 expression, were associated with an increased relative risk of RM (p < 0.0001).

Conclusions:

  • Elevated endometrial levels of uNK cells and FoxP3+ Tregs, coupled with diminished PGRMC1 expression, are implicated as potential contributors to the development of recurrent miscarriage.
  • These findings highlight specific immunological and molecular factors that may be crucial in understanding and potentially managing RM.