Leukemia inhibitory factor (LIF) production by human decidua and its relationship with pregnancy hormones

The expression of leukemia inhibitory factor (LIF) by murine uterus was shown to be regulated by maternal hormones and was not dependent on the presence of an embryo. The objective of this study was to investigate whether in humans the secretion of LIF during early pregnancy is under maternal control and whether its production is correlated with pregnancy hormones, progesterone and beta-human chorionic gonadotropin (beta hCG). To exclude the possibility of paracrine interaction of decidua with trophoblast, we examined the secretion of LIF in women with extrauterine pregnancy. The present study was designed as a prospective, blinded, clinical and immunobiochemical study. The endometrial biopsies were performed on 12 women during surgery for ectopic pregnancy. On the same day, the level of progesterone and beta hCG in maternal plasma was examined. LIF concentration was determined in supernatants taken from cultured decidual explants. LIF production by decidual culture explants was found in all women with an ectopic pregnancy (Median 5015 pg, range 1389-19,304 pg). There was no correlation between the LIF production and the term of pregnancy, or with the level of circulated beta hCG (p > 0.05). However, when the concentration of progesterone in circulating plasma was less than 5 ng/ml, the secretion of LIF was 2.3-fold higher as compared to women who had progesterone levels of more than 5 ng/ml (p < 0.01). Therefore, we conclude that LIF is actively produced by human decidua and that the production of this cytokine does not depend on the presence of fetotrophoblast. This study demonstrates for the first time that progesterone downregulates the secretion of LIF in the decidua during early pregnancy.