Induction of prostaglandin E2 production by leukemia inhibitory factor promotes migration of first trimester extravillous trophoblast cell line, HTR-8/SVneo

BACKGROUND: The invasion of first trimester extravillous trophoblast (EVT) to decidua is an important event in placentation. Leukemia inhibitory factor (LIF) is an essential factor for mouse implantation, and it is reported that LIF may be involved in human first trimester EVT invasion. Prostaglandin E 2 (PGE 2 ) is also known as a critical factor for first trimester EVT invasion. In this study, we investigated the role of LIF in PGE 2 production and EVT invasion using a human first trimester EVT cell line, HTR-8/SVneo. METHODS and RESULTS: Co-stimulation with LIF and IL-1β induced higher amounts of PGE 2 production and further migration of HTR-8/SVneo cells compared with that by stimulation with LIF or IL-lp alone. Enhanced PGE 2 production was most probably due to the enhanced expression of cyclooxygenase-2 (COX-2) and microsomal PGE synthase-1 (mPGES-1). PGE 2 produced by HTR-8/SVneo cells promoted the migration of HTR-8/SVneo cells. A COX-2 inhibitor suppressed PGE 2 production and the migration of HTR-8/SVneo cells. Agonists to PGE 2 receptors, EP1, EP2 and EP4, promoted the migration of HTR-8/SVneo cells. Moreover, stimulation with LIF up-regulated EP1, EP2 and EP4 expression in HTR-8/SVneo cells. CONCLUSIONS: It is suggested that LIF participates in placentation through EVT invasion by up-regulating PGE 2 production and PGE 2 receptor expression in first trimester EVT.