CONICET | Buscador de Institutos y Recursos Humanos

An intricate molecular dialogue between trophoblast and uterus initiates the process of implantation, by which the embryo attaches to the lining of the uterus. After implantation, trophoblast cells begin a proliferative, migrating and invasive process infiltrating the decidua, remodeling uterine vasculature and connecting the mother blood stream with the fetus. These events are accomplished by molecular and cellular interactions controlled by the maternal-fetal interface microenvironment and may fail in certain obstetric complications such as preeclampsia, intrauterine growth restriction and implantation failure.Several years ago, it has been observed that there is a change in the lipid composition at the luminal epithelium adjacent to the area where the blastocyst is attached. This change is interpreted as a mobilization of precursors for the synthesis of lipid molecules that participate in angiogenesis and in the transformation of endometrial fibroblasts into decidual cells. Hence, novel insights with respect to roles played by the participation of lipids in the establishment of pregnancy have sparked a renewed interest in understanding them no longer as simple structural components of the membranes but as reproductive bioactive mediators.In this sense, lysophosphatidic acid (LPA) and prostaglandins play a major role in embryo implantation. LPA has pleiotropic functions by binding to six G-protein coupled receptors. Prostaglandins have a pivotal role in decidualization and vascularization, two main processes during trophoblast migration and invasion. We have previously reported that LPA augments the production of cyclooxygenase-2 derived prostaglandin E2 in the rat uterus during the window of implantation. Trophoblast cells are the main source of LPA in human first trimester, suggesting that LPA actively participates in trophoblast functions.Defects in trophoblast migration and invasion are particularly vulnerable to failure during embryo implantation resulting in pregnancy complications. Therefore, we aimed to investigate the role of LPA on human first trimester trophoblast´s functions and its interaction with prostaglandin E2.To achieve our experiments, we use a well-known immortalized human first trimester trophoblast cell line HTR-8/SVneo. We design a pharmacological strategy using selective and broad range LPA receptors antagonists and cyclooxygenase inhibitors. First, we characterize the mRNA expression of LPA receptors and the enzyme Lysophospholipase-D, the main enzyme involved in LPA synthesis and its principal source during gestation are the placental trophoblast. We observed that LPA stimulates both invasion and migration through LPA1-LPA4 receptors (p