The human endometrium is exposed to cyclical fluctuations of ovarian-derived sex steroids resulting in proliferation, differentiation (decidualization), and menstruation. An influx of leukocytes (up to 15% macrophages) occurs during the latter stages of the menstrual cycle, including menses. We believe the endometrial macrophage is likely to play an important role during the menstrual cycle, especially in the context of tissue degradation (menstruation), which requires regulated repair, regeneration, and phagocytic clearance of endometrial tissue debris to re-establish tissue integrity in preparation for fertility. The phenotype and regulation of the macrophage within the endometrium during the menstrual cycle and interactions with other cell types that constitute the endometrium are currently unknown and are important areas of study. Understanding the many roles of the endometrial macrophage is crucial to our body of knowledge concerning functionality of the endometrium as well as to our understanding of disorders of the menstrual cycle, which have major impacts on the health and well-being of women.

Endometriosis affects more than 10% of women, causing significant pain and morbidity. It is also a significant cause of infertility. The aetiology of the disease remains an enigma, and the mechanisms responsible for the associated infertility are unclear. A role for immune cells in endometriosis has been postulated, with attention directed towards natural killer (NK) cells and macrophages. NK cells kill tumours and infected cells but also have roles in tissue remodelling in several organs including the uterus and are key to successful pregnancy. Here, we explore evidence (from peer-reviewed published articles) of phenotypic and functional abnormalities in NK cell subpopulations of women with endometriosis. It is clear that peripheral blood NK cells and peritoneal NK cells have reduced cytotoxic function in women with endometriosis. Uterine NK cells have a vital role in infertility, but very little research has been carried out in this area. We propose that abnormal u NK cell activity may contribute to the pathogenesis of endometriosis and its associated infertility and that future research should focus on this complex area.

We have shown that women with endometriosis have low levels of endometrial SCF, which we hypothesize contributes to abnormal maturation of local uNK cell populations. This defect may also compromise embryo implantation and hence contribute to endometriosis-associated infertility. SCF replacement may be a new therapeutic approach.