Reelin regulates migration and differentiation of extravillous trophoblastic cells: Implications for Preeclampsia

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dc.catalogadorpva
dc.contributor.authorSommer Venegas, Nicole Antonia
dc.contributor.authorPacheco Zapata, Aníbal Alejandro
dc.contributor.authorCarvajal C., Jorge A.
dc.contributor.authorOlguín Marín, Hugo César
dc.contributor.authorLeiva, Andrea
dc.contributor.authorGutierrez, Jaime
dc.contributor.authorMarzolo Canales, María Paz
dc.date.accessioned2025-10-30T19:17:29Z
dc.date.available2025-10-30T19:17:29Z
dc.date.issued2025
dc.description.abstractBackground ApoER2/LRP8 is a receptor highly expressed in the placenta; however, its physiological role in this organ is little known. Reelin, an ApoER2 ligand, is an extracellular glycoprotein that participates in neuronal polarization, migration and differentiation, hence having a central role in the central nervous system (CNS) development. Upon binding to ApoER2, Reelin triggers a complex signaling pathway that regulates cytoskeleton dynamics, gene expression and transcript translation. This paper aimed to determine whether the ApoER2/Reelin signaling pathway has roles in cellular processes related to placentation.Results We characterized the Reelin-ApoER2 system using first-trimester extravillous trophoblast (EVT) cell lines. The receptor is present at the cell surface and in the nucleus. EVT cells Swan 71 responded to Reelin exposure by activating the PI3K-Akt and increasing ApoER2 levels. Additionally, a dual role of Reelin through PI3K was established in these cells, as it enhanced trophoblastic migration at 2% O2 (to mimic the hypoxic physiologic conditions of trophoblastic migration) and its differentiation to an endothelial-like phenotype at 21% O2. Migration was also stimulated, independent of PI3K, when cells were exposed to normoxic culture conditions (21% of O2) or chemically induced hypoxia (by CoCl2). We propose that physiologically, during the first trimester, Reelin, together with its ApoER2 receptor, could act by stimulating trophoblastic migration and differentiation. Interestingly, Reelin also modulated hypoxia-inducible factor HIF1-α levels. Both ApoER2 and Reelin were detected in human term placentas from normal and preeclampsia with severe features (PE-SF) pregnancies. Reelin plasma levels were lower in severe PE patients already in the first semester of pregnancy, before the appearance of PE symptoms.Conclusions Reelin could be involved in placentation, playing roles in EVT migration and differentiation. The reduction in maternal Reelin levels detected at early pregnancy could be a potential biomarker for PE.
dc.fechaingreso.objetodigital2025-10-30
dc.format.extent35 páginas
dc.fuente.origenORCID
dc.identifier.doi10.21203/rs.3.rs-7934067/v1
dc.identifier.eissn2693-5015
dc.identifier.urihttps://doi.org/10.21203/rs.3.rs-7934067/v1
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/106448
dc.information.autorucFacultad de Ciencias Biológicas; Sommer Venegas, Nicole Antonia; S/I; 1066798
dc.information.autorucFacultad de Ciencias Biológicas; Pacheco Zapata, Aníbal Alejandro; S/I; 1050264
dc.information.autorucEscuela de Medicina; Carvajal C., Jorge A.; 0000-0001-6875-7825; 3345
dc.information.autorucFacultad de Ciencias Biológicas; Olguín Marín, Hugo César; 0000-0003-4072-7776; 8240
dc.information.autorucFacultad de Ciencias Biológicas; Marzolo Canales, María Paz; S/I; 72595
dc.language.isoen
dc.nota.accesocontenido completo
dc.revistaResearch Square
dc.rightsacceso abierto
dc.rights.licenseAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectApoER2
dc.subjectEVT
dc.subjectEndothelial EVT
dc.subjectHypoxia
dc.subjectPlacentation
dc.subjectPreeclampsia
dc.subjectTrophoblast
dc.subjectReelin
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.subject.ods03 Good health and well-being
dc.subject.odspa03 Salud y bienestar
dc.titleReelin regulates migration and differentiation of extravillous trophoblastic cells: Implications for Preeclampsia
dc.typepreprintp
sipa.codpersvinculados1066798
sipa.codpersvinculados1050264
sipa.codpersvinculados3345
sipa.codpersvinculados8240
sipa.codpersvinculados72595
sipa.trazabilidadORCID;2025-10-27
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