The production of leukaemia inhibitory factor by human endometrium: presence in uterine flushings and production by cells in culture

TLDR

The study investigated the production of LIF by cultured human epithelial and stromal endometrial cells. LIF concentrations were measured in uterine flushings from normal fertile women, women with unexplained infertility, and recurrent miscarriage, and LIF production was assessed in cultured epithelial and stromal endometrial cells. LIF was undetectable in early luteal‑phase flushings but rose to peak at day LH+12, was significantly lower in women with unexplained infertility, was not produced by stromal cells, varied with cycle stage in epithelial cells (higher in late proliferative/early secretory), decreased modestly with high progesterone/estradiol, and these findings suggest a role for LIF in embryo implantation.

Abstract

The concentration of leukaemia inhibitory factor (LIF) was measured in uterine flushings obtained from normal fertile women, from women with unexplained infertility and from women who suffered recurrent miscarriage. In normal fertile women, LIF was not detected in flushings obtained on days luteinizing hormone (LH)+0 to LH+6 of the cycle, but concentrations gradually increased from day LH+7 to a maximum at day LH+12. The amount of LIF in flushings obtained from women with unexplained infertility was significantly lower than in those from normal fertile women on day LH+10 (P < 0.05). The production of LIF by cultured human epithelial and stromal cells was also investigated. LIF was not detectable in the supernatants of cultured stromal cells. Basal LIF production by epithelial cells varied according to the stage in the cycle at which the biopsy was taken. Significantly more LIF was produced by epithelial cells from late proliferative and early secretory endometrium compared with amounts produced by cells from early proliferative (P < 0.001) and late secretory (P < 0.01) endometrium. High doses of progesterone and oestradiol caused a small decrease in epithelial cell LIF production: the combined effect of progesterone and oestradiol (P < 0.01) was greater than the effect of either steroid alone (P < 0.05). The results show, for the first time, the capability of human endometrium to produce LIF in vivo. The fact that maximum LIF concentrations are present at implantation and that decreased concentrations occur in women with unexplained infertility suggest the importance of this cytokine in embryo implantation.