Role of Uterine Natural Killer Cells in Women with Infertility and Associated Endometriosis: A Case Control Study

Abstract

Endometriosis is characterized by the presence, outside the endometrial cavity, of tissue that is morphologically and biologically similar to normal endometrium. This ectopic endometrial tissue responds to ovarian hormones undergoing cyclical changes similar to those seen in eutopic endometrium. The clinical diagnosis of endometriosis is primarily made at the time of laparoscopy, although there is increasing support for empirical treatment with laparoscopy if symptoms persist. The classic appearance is of blue-black lesions, but many subtler appearances are now recognized. Endometriosis is present in 20-40% of women who complain of subfertility, although it can be found in 5% of fertile women. Postulated explanations include intraperitoneal inflammation, immunological factors, unruptured luteinized follicles, and an increase in the rate of miscarriage. Uterine natural killer (NK) cells are the predominant leukocyte population in normal human endometrium. Approximately 70–80% of uterine NK cells are characterized as CD56brightCD16-. Their content varies throughout the normal menstrual cycle, likely due to recruitment of peripheral NK cells and/or in utero proliferation/differentiation of stem uterine NK cells. Another minor subpopulation of uterine NK cells, characterized asCD56dimCD16+, displays cytotoxic activity toward the extravillous trophoblast and autologous endometrial cells and may create a hostile environment for implantation. Successful embryo implantation requires a receptive endometrium, a functional embryoat the blastocyst developmental stage and a synchronized dialog between maternal and embryonic tissues. Another minor subpopulation of uterine NK cells, characterized asCD56dimCD16+, displays cytotoxic activity toward the extravillous trophoblast and autologous endometrial cells and may create a hostile environment for implantation. Successful embryo implantation requires a receptive endometrium, a functional embryoat the blastocyst developmental stage and a synchronized dialog between maternal and embryonic tissues. Recently, it was concluded that women who have larger populations of cytotoxic CD16+ uterine NK cells and/or higher populations of CD56dimcells may be at greater risk of infertility disorders resulting from an inflammatory environment occurring during implantation or later during decidualization. Our study put the hypothesis that: the expression of CD56 and CD16 uterine natural killer cells in the endometrium is not correlated to infertility associated with endometriosis. So in a case control study was designed with 130 ladies divided into three groups. Group I was included 100 patients with infertility with endometriosis, Group ΙΙ was included 20 healthy women and Group ΙIΙ was included 10 fertile women with endometriosis. Endometrial sample taken was prepared and immune-stained for CD56and CD16. We had found that the expression of CD56dim/CD16+ uNK cells population in endomtreotic patients was high in comparison to those with endometriosis. Explaining the possible link between its inflammatory action and pathogenesis of endometriosis. Our study concluded as well that CD56/CD16 expression is high among infertile women. CD56dim/CD16+ uNK cells were found in all infertile patients.