CONICET | Buscador de Institutos y Recursos Humanos

Introduction: An intricate molecular dialogue between trophoblast and uterus initiates the process of implantation. After the embryo attaches to the lining of the uterus, trophoblast cells begin a proliferative, migrating and invasive process infiltrating the decidua and remodeling uterine vasculature.Novel insights about the role played by lipids in the establishment of early pregnancy have sparked a renewed interest in understanding them as reproductive bioactive molecules. In this sense, lysophosphatidic acid (LPA) and prostaglandin E2 (PGE2) are well-known mediators of embryo implantation. LPA has pleiotropic functions by binding to six G-protein coupled receptors. Besides, PGE2 exerts a pivotal participation in decidualization and vascular remodeling. In the last years, MRP4 transporter has been described as an additional checkpoint that regulates PGE2 efflux.Trophoblast migration is accomplished by molecular and cellular interactions controlled by the maternal-fetal interface microenvironment. Defects in this mechanism might contribute to certain obstetric complications. We have previously reported that LPA augments trophoblast cell migration and stimulates PGE2 production. Therefore, we aimed to investigate the interaction between LPA and MRP4 in human first trimester trophoblast cell migration.Methods: HTR-8/SVneo cell line (H8) was used as a model of human first trimester extravillous trophoblast. A pharmacological in vitro strategy was designed. H8 cells were incubated with LPA 5x10-5M, LPA+BMT (10-5M, an LPA1 antagonist), LPA+AH6809 (10-6M, an EP1/EP2 antagonist), LPA+AH 23848 (10-6M, an EP4 antagonist) or LPA+MK-571 (10-5M, an MRP4 inhibitor) and assayed for migration (wound healing assay, 18h). MRP4 expression was characterized by PCR and western blot.Results: LPA+BMT completely reversed LPA effect on trophoblast migration (p