AQUAPORIN-3 AND CAVEOLAE IN THE ETIOLOGY OF PREECLAMPSIA

DAMIANO, ALICIA E

Chillán

Congreso; III Meeting on Research and Innovation in Vascular Health; V Meeting on Hypertension in Pregnancy; 2019

Grivas Health

During placentation, trophoblast cells differentiate to invasive extravillous trophoblast (EVT) or fuse to form the syncytium. Alterations in this highly-synchronized process are associated with preeclampsia.Aquaporin-3 (AQP3) is the most abundant AQP expressed in chorionic villi from the first trimester and its expression persists in term placentas.It is well-documented that the localization of numerous channels in caveolae is crucial for their activity. Caveolae are plasma membrane invaginations, rich in cholesterol and sphingomyelin and caveolin-1 (Cav-1) is the main integral membrane protein of these subdomains. In other tissues, several data consistently support a role of caveolae in cell migration and differentiation. Apart from the classical functions in transcellular water transport, recent studies revealed that AQPs may also cooperate in these processes.Previously, we reported a decreased expression of Cav-1 in syncytiotrophoblast from preeclamptic placentas, which was associated with alterations in the membrane lipid composition required for the formation of caveolae. Recently, we also found that AQP3 was reduced in these placentas.However, the abnormal expression of AQP3 and Cav-1 were described at the end of gestation, when preeclampsia is already established. Therefore, we explored the role of AQP3 and caveolae in the migration, invasion and endovascular differentiation of EVT cells during placentation. In-silico analysis of AQP3 protein revealed a putative Cav-1 binding site. In addition, immunoprecipitation and double immunofluorescence assays confirmed that AQP3 co-localized with Cav-1 in EVT cells. We also found that the specific silencing or the functional blocking of AQP3 and caveolae disruption significantly attenuated migration but not invasion of EVT cells. Surprisingly, the disruption of caveolae enhanced EVT endovascular differentiation. Thus, we propose that an intact caveola is required for the normal AQP3 expression and function and any perturbations might result in an aberrant transformation of the maternal spiral arteries leading to serious pregnancy disorders such as preeclampsia.