Significance of imbalance of endometrial immune cells in endometrial receptivity and its link to reproductive outcome

Abstract

Background. Disturbed endometrial immune reactivity/receptivity due to the imbalance of im­mune cells-different subpopulations of endometrial lymphocytes, has been regarded as one of the most controversial issues in reproductive immunology. It has been associated with unfavourable outcomes of pregnancy, among them recurrent pregnancy loss, repeated implantation failure, and “Great Obstetrical Syndromes” (pre-eclampsia, fetal growth retardation, preterm delivery, stillbirth). Uterine Natural Killer cells are major immune cells present in the endometrium and key players in tolero­genic immune mechanisms at the maternal-fetal interface during implantation and placentation in the first trimester of pregnancy. There is a growing interest worldwide in understanding the potential role of altered number and function of endometrial lymphocyte subpopulations to­wards the reproductive outcome. Especially, the involvement of disturbed ratio between the cytotoxic and immunomodulatory phenotypes of uterine Natural Killer cells has been sharply debated.  Unfortunately, there is still a need to advance evidence-based immunological diagnostics, translate it into clinical practice and meet the clinicians’ requirements for choosing individualized immunological treatment options.

Aim: This review article aims to summarize the current knowledge on dysregulated endometrial immunological events at the maternal-fetal interface, with special emphasis on the role of different subpopulations of uterine Natural Killer cells in the reproductive outcome.  

Method: the literature regarding this issue was searched through the following electronic databases: Pubmed, Medline, Cochrane Library, Web of Science, EMBASE in the period of 2000-2019yy.

Conclusions: Unique, sensitive balance of endometrial immune cells and an adequate immunological “cross-talk” at the maternal-fetal interface have a pivotal role in the survival of the semi-allogeneic fetus. Disturbed endometrial immune receptivity due to the inadequate number and function of endometrial immune cells-especially uterine Natural Killer cells, is one of the most controversial immunological pathways, that  associated with adverse reproductive outcome. The current ongoing challenge for researchers is to find out highly informative endometrial immune parameters to predict the potential risk for subsequent pregnancy