Nuevos enfoques del proceso de vascularización en la gestación temprana. Rol del LPA y su receptor LPA3 en la vascularización de la interfase materno-fetal.

BELTRAME, JS; SORDELLI, MS; FRANCHI ANA M; RIBEIRO MARÍA LAURA

CABA, Argentina.

Congreso; X Congreso de la Sociedad Argentina de Endocrinología Ginecológica y Reproductiva (SAEGRE),; 2016

Nuevos enfoques del proceso de vascularización en gestación temprana. Beltrame JS, Sordelli MS, Ribeiro ML.Successfulimplantation and placentation requires that extravillous cytotrophoblastacquires an endovascular phenotype and remodels uterine spiral arteries.Defects in this mechanism correlate with severe obstetric complications asimplantation failure and preeclampsia. Lysophosphatidic acid (LPA) participatesin embryo implantation and contributes to vascular physiology in differentbiological systems. However, the role of LPA on trophoblast endovasculartransformation has not been studied. Due to difficulties in studying humanpregnancy in vivo, we adopted apharmacological approach in vitro toinvestigate LPA action in various aspects of trophoblast endovascular response,such as the formation of endothelial capillary-like structures, migration andproliferation. The HTR-8/SVneo cell line established from human first trimestercytotrophoblast was used to model the acquisition of the endovascular phenotypeby the invading trophoblast. LPA increased HTR-8/SVneo tube formation,migration (wound healing assay and phalloidin staining) and proliferation (MTTassay). LPA G protein-coupled receptors, LPA1 and LPA3,were expressed in HTR-8/SVneo. By using selective antagonists, we showed thatenhanced tubulogenesis was mediated by LPA3. In addition,cyclooxygenase-2 and inducible nitric oxide synthase pathways participated inLPA-stimulated tubulogenesis. Inducible nitric oxide synthase was activateddownstream cyclooxygenase-2. Furthermore, prostaglandin E2 and a nitric oxidedonor (SNAP) increased trophoblast tube formation in a concentration-dependentmanner. Finally, we observed that cyclooxygenase-2 and inducible nitric oxidesynthase were localized in the nucleus, and LPA did not modify their cellulardistribution. Our results show that LPA-triggered regulatory pathways promotetrophoblast endovascular response invitro, suggesting a new role for LPA during spiral artery remodeling at thematernal-fetal interface.