Expression of leukaemia inhibitory factor and interleukin 15 in endometrium of women with recurrent implantation failure after IVF; correlation with the number of endometrial natural killer cells

• Published in: Human reproduction (Oxford) 2012-07, Vol.27 (7), p.1946-1954
• Main Authors: Mariee, N., Li, T.C., Laird, S.M.
• Format: Article
• Language: English
• Subjects: Adult; Biological and medical sciences; Biopsy; Case-Control Studies; Cell Proliferation; Embryo Implantation; Endometrium - metabolism; Epithelial Cells - cytology; Female; Fertility; Fertilization in Vitro; Gene Expression Regulation; Gynecology. Andrology. Obstetrics; Humans; Infertility, Female - pathology; Interleukin-15 - biosynthesis; Interleukin-15 - metabolism; Killer Cells, Natural - cytology; Leukemia Inhibitory Factor - biosynthesis; Medical sciences; Phenotype; Pregnancy; Pregnancy Outcome
• ISSN: 0268-1161; 1460-2350
• DOI: 10.1093/humrep/des134

BACKGROUND Several studies have suggested that endometrial interleukin 15 (IL-15) and the leukaemia inhibitory factor (LIF) may be important in embryo implantation. IL-15 is postulated to play a role in the control of uterine natural killer (uNK) cell proliferation and function, and uNK cells are also known to play a role in implantation. The aims of this study was to (1) compare endometrial levels of IL-15 and the LIF in women with recurrent implantation failure (RIF) after IVF with those in fertile women (controls) and (2) examine the relation of IL-15 and LIF levels to the uNK cell number. METHODS We investigated IL-15 and LIF in precisely timed endometrial biopsies (days LH + 7-LH + 9, where the day of the LH surge is LH + 0) obtained from control women (n = 15) and women with RIF (n = 45) by immunohistochemistry. A semi-quantitative analysis was performed by the H-score analysis of staining intensity in the stroma, glandular epithelium and luminal epithelium, separately. We also correlated expression of LIF and IL15 with uNK cell numbers (obtained in an earlier study of the same samples). RESULTS The quantity of the LIF protein in endometrial glandular epithelium in women with RIF [median and range; 179 (70–365)] was lower (P = 0.01) than in control women [median and range; 247 (120–287)]. In contrast, the level of the IL-15 protein in the stroma in women with RIF [median and range; 90 (0–175)] was higher (P = 0.009) than in control women [median and range; 60 (15–150)]. There was a significant correlation between the uNK cell number and stromal expression of IL-15 (r = 0.427, P = 0.001). No correlation between the LIF expression in any compartment and the uNK cell number was seen. CONCLUSIONS The results show an altered expression of LIF and IL-15 in the endometrium of women with RIF. Despite the limitation of not identifying uNK cells by phenotypic markers, the correlation between the uNK cell number and the stromal cell IL-15 suggests that IL-15 may play a role in the control of endometrial uNK cell function or proliferation.