PEMEMBREP

Placental dysfunction induces placental diseases. Among those, preeclampsia (PE) is prominent and induces hypertension in the mother as well as proteinuria, sometimes threatening the life of the mother and of the baby, as well as their present and future well-being. PE is often complicated by intra-uterine growth restriction (iUGR), a failure of the foetus to reach its normal growth potential. Both diseases affect about 10% of pregnancies and constitute therefore a considerable worldwide health concern. At the center of these diseases is the function of the original cell of the placenta, the trophoblast, and of its fusion product, the syncytiotrophoblast. Syncytialization involves membrane rearrangements frequently encountered in the process of membrane repair, a mechanism that allows the cell to survive various stresses able to destroy locally their membrane (in the case of the syncytiotrophoblast, in particular, shear stress from contact with the blood appears to be a major regulatory factor). While PE and iUGR have complex etiologies, in some groups of patients the disease is explained by defects in the repair machinery, leading to accelerated ageing of the syncytiotrophoblast, induction of abnormal levels of oxidative and nitrosative stress, and eventually to placental dysfunction or even local necrosis. In the placental life, membranes are also essential in releasing extracellular vesicles that will allow a molecular dialogue to be installed between mother and fetus. The present project will make a rational link between membrane dynamics of the trophoblast and placental dysfunction. It is made possible by the collaboration of three teams: the first one is expert in placental physiology, genetics and epigenetics, the second in membrane dynamics, and the third one in developing cell models through gene-editing approaches.