Decidual leukemia inhibitory factor production and action on human chorionic gonadotropin secretion at different stages of gestation in vitro.

Abstract

Leukemia inhibitory factor (LIF) is a pleiotropic cytokine essential for uterine blastocyst implantation. We investigated human LIF production and action on human chorionic gonadotropin (hCG) secretion at different stages of gestation. Decidual and chorionic tissues were obtained at the first and second trimesters of pregnancy, and at term. Decidual and trophoblast cells were isolated and cultured separately and medium LIF or hCG levels were measured by radioimmunoassay. Decidual cells derived from the first and second trimester, and term were cultured for 72 h in serum-containing medium and produced 374 +/- 162 (mean +/- SEM), 140 +/- 14 and 466 +/- 134 ngLIF/mg protein, respectively. Pregnant mare serum gonadotropin (10 U/ml) did not affect LIF production from first-trimester decidual cells, but inhibited second-trimester LIF production to 37% of that of controls (p < 0.05), and stimulated LIF production from term decidual cells to 125% of that of controls (p < 0.05). First-trimester trophoblast cells treated with 10 nmol/l hLIF for 72 h in serum-free medium increased hCG secretion by 125% (p = 0.05). Conversely, hLIF dose-dependently inhibited basal and cAMP-stimulated hCG secretion in trophoblasts derived during the second trimester and at term, as well as in cultured JEG-3 choriocarcinoma cells. LIF exhibited more potent inhibitory action in the second trimester, maximally reducing hCG production by 37% from that of control values (p < 0.05) at a dose of 10 nmol/l. These findings indicate that (1) LIF is produced by decidual cells throughout pregnancy and may play a different regulatory role of hCG production at different stages of gestation; and (2) gonadotropin synthesized in trophoblasts may, in part, regulate LIF production through a paracrine pathway.