Pregnancy-Induced High Plasma Levels of Soluble Endoglin in Mice Lead to Preeclampsia Symptoms and Placental Abnormalities

[EN]Preeclampsia is a pregnancy-specific disease of high prevalence characterized by the onset of hypertension, among other maternal or fetal signs. Its etiopathogenesis remains elusive, but it is widely accepted that abnormal placentation results in the release of soluble factors that cause the cli...

Full description

Bibliographic Details
Authors: Pérez Roque, Lucía, Núñez Gómez, Elena, Rodríguez Barbero, Alicia, Bernabeu, Carmelo, López-Novoa, José M., Pericacho Bustos, Miguel
Format: article
Publication Date:2020
Country:España
Institution:Universidad de Salamanca (USAL)
Repository:GREDOS. Repositorio Institucional de la Universidad de Salamanca
OAI Identifier:oai:gredos.usal.es:10366/154763
Online Access:http://hdl.handle.net/10366/154763
Access Level:Open access
Keyword:Placenta
Preeclampsia
Soluble endoglin
Animal model
Murine model
Pre-Eclampsia
Pregnancy
Trophoblasts
Fetal Growth Retardation
Placenta Diseases
Animals
Humans
Mice
Vascular Diseases
animales
humanos
embarazo
ratones
enfermedades vasculares
enfermedades placentarias
preeclampsia
trofoblastos
retraso del crecimiento fetal
id ES_a54025e83e2d9ad4e54d0dd89069927e
oai_identifier_str oai:gredos.usal.es:10366/154763
network_acronym_str ES
network_name_str España
repository_id_str
spelling Pregnancy-Induced High Plasma Levels of Soluble Endoglin in Mice Lead to Preeclampsia Symptoms and Placental AbnormalitiesPérez Roque, LucíaNúñez Gómez, ElenaRodríguez Barbero, AliciaBernabeu, CarmeloLópez-Novoa, José M.Pericacho Bustos, MiguelPlacentaPreeclampsiaSoluble endoglinAnimal modelMurine modelPre-EclampsiaPregnancyTrophoblastsFetal Growth RetardationPlacenta DiseasesAnimalsHumansMiceVascular Diseasesanimaleshumanosembarazoratonesenfermedades vascularesenfermedades placentariaspreeclampsiatrofoblastosretraso del crecimiento fetal[EN]Preeclampsia is a pregnancy-specific disease of high prevalence characterized by the onset of hypertension, among other maternal or fetal signs. Its etiopathogenesis remains elusive, but it is widely accepted that abnormal placentation results in the release of soluble factors that cause the clinical manifestations of the disease. An increased level of soluble endoglin (sEng) in plasma has been proposed to be an early diagnostic and prognostic biomarker of this disease. A pathogenic function of sEng involving hypertension has also been reported in several animal models with high levels of plasma sEng not directly dependent on pregnancy. The aim of this work was to study the functional effect of high plasma levels of sEng in the pathophysiology of preeclampsia in a model of pregnant mice, in which the levels of sEng in the maternal blood during pregnancy replicate the conditions of human preeclampsia. Our results show that wild type pregnant mice carrying human sEng-expressing transgenic fetuses (fWT(hsEng+)) present high plasma levels of sEng with a timing profile similar to that of human preeclampsia. High plasma levels of human sEng (hsEng) are associated with hypertension, proteinuria, fetal growth restriction, and the release of soluble factors to maternal plasma. In addition, fWT(hsEng+) mice also present placental alterations comparable to those caused by the poor remodeling of the spiral arteries characteristic of preeclampsia. In vitro and ex vivo experiments, performed in a human trophoblast cell line and human placental explants, show that sEng interferes with trophoblast invasion and the associated pseudovasculogenesis, a process by which cytotrophoblasts switch from an epithelial to an endothelial phenotype, both events being related to remodeling of the spiral arteries. Our findings provide a novel and useful animal model for future research in preeclampsia and reveal a much more relevant role of sEng in preeclampsia than initially proposed.Ministerio de Economía y Competitividad, Instituto de Salud Carlos III, Junta de Castilla y León, Fundación Renal Iñigo Álvarez de Toledo, Kidney Research Network REDINREN, Consejo Superior de Investigaciones CientíficasMDPI202420242020info:eu-repo/semantics/articlehttp://hdl.handle.net/10366/154763reponame:GREDOS. Repositorio Institucional de la Universidad de Salamancainstname:Universidad de Salamanca (USAL)InglésSAF2010-15881SAF2013-45784-RPI16/00460201920E022Attribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:gredos.usal.es:10366/1547632026-06-07T06:28:51Z
dc.title.none.fl_str_mv Pregnancy-Induced High Plasma Levels of Soluble Endoglin in Mice Lead to Preeclampsia Symptoms and Placental Abnormalities
title Pregnancy-Induced High Plasma Levels of Soluble Endoglin in Mice Lead to Preeclampsia Symptoms and Placental Abnormalities
spellingShingle Pregnancy-Induced High Plasma Levels of Soluble Endoglin in Mice Lead to Preeclampsia Symptoms and Placental Abnormalities
Pérez Roque, Lucía
Placenta
Preeclampsia
Soluble endoglin
Animal model
Murine model
Pre-Eclampsia
Pregnancy
Trophoblasts
Fetal Growth Retardation
Placenta Diseases
Animals
Humans
Mice
Vascular Diseases
animales
humanos
embarazo
ratones
enfermedades vasculares
enfermedades placentarias
preeclampsia
trofoblastos
retraso del crecimiento fetal
title_short Pregnancy-Induced High Plasma Levels of Soluble Endoglin in Mice Lead to Preeclampsia Symptoms and Placental Abnormalities
title_full Pregnancy-Induced High Plasma Levels of Soluble Endoglin in Mice Lead to Preeclampsia Symptoms and Placental Abnormalities
title_fullStr Pregnancy-Induced High Plasma Levels of Soluble Endoglin in Mice Lead to Preeclampsia Symptoms and Placental Abnormalities
title_full_unstemmed Pregnancy-Induced High Plasma Levels of Soluble Endoglin in Mice Lead to Preeclampsia Symptoms and Placental Abnormalities
title_sort Pregnancy-Induced High Plasma Levels of Soluble Endoglin in Mice Lead to Preeclampsia Symptoms and Placental Abnormalities
dc.creator.none.fl_str_mv Pérez Roque, Lucía
Núñez Gómez, Elena
Rodríguez Barbero, Alicia
Bernabeu, Carmelo
López-Novoa, José M.
Pericacho Bustos, Miguel
author Pérez Roque, Lucía
author_facet Pérez Roque, Lucía
Núñez Gómez, Elena
Rodríguez Barbero, Alicia
Bernabeu, Carmelo
López-Novoa, José M.
Pericacho Bustos, Miguel
author_role author
author2 Núñez Gómez, Elena
Rodríguez Barbero, Alicia
Bernabeu, Carmelo
López-Novoa, José M.
Pericacho Bustos, Miguel
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Placenta
Preeclampsia
Soluble endoglin
Animal model
Murine model
Pre-Eclampsia
Pregnancy
Trophoblasts
Fetal Growth Retardation
Placenta Diseases
Animals
Humans
Mice
Vascular Diseases
animales
humanos
embarazo
ratones
enfermedades vasculares
enfermedades placentarias
preeclampsia
trofoblastos
retraso del crecimiento fetal
topic Placenta
Preeclampsia
Soluble endoglin
Animal model
Murine model
Pre-Eclampsia
Pregnancy
Trophoblasts
Fetal Growth Retardation
Placenta Diseases
Animals
Humans
Mice
Vascular Diseases
animales
humanos
embarazo
ratones
enfermedades vasculares
enfermedades placentarias
preeclampsia
trofoblastos
retraso del crecimiento fetal
description [EN]Preeclampsia is a pregnancy-specific disease of high prevalence characterized by the onset of hypertension, among other maternal or fetal signs. Its etiopathogenesis remains elusive, but it is widely accepted that abnormal placentation results in the release of soluble factors that cause the clinical manifestations of the disease. An increased level of soluble endoglin (sEng) in plasma has been proposed to be an early diagnostic and prognostic biomarker of this disease. A pathogenic function of sEng involving hypertension has also been reported in several animal models with high levels of plasma sEng not directly dependent on pregnancy. The aim of this work was to study the functional effect of high plasma levels of sEng in the pathophysiology of preeclampsia in a model of pregnant mice, in which the levels of sEng in the maternal blood during pregnancy replicate the conditions of human preeclampsia. Our results show that wild type pregnant mice carrying human sEng-expressing transgenic fetuses (fWT(hsEng+)) present high plasma levels of sEng with a timing profile similar to that of human preeclampsia. High plasma levels of human sEng (hsEng) are associated with hypertension, proteinuria, fetal growth restriction, and the release of soluble factors to maternal plasma. In addition, fWT(hsEng+) mice also present placental alterations comparable to those caused by the poor remodeling of the spiral arteries characteristic of preeclampsia. In vitro and ex vivo experiments, performed in a human trophoblast cell line and human placental explants, show that sEng interferes with trophoblast invasion and the associated pseudovasculogenesis, a process by which cytotrophoblasts switch from an epithelial to an endothelial phenotype, both events being related to remodeling of the spiral arteries. Our findings provide a novel and useful animal model for future research in preeclampsia and reveal a much more relevant role of sEng in preeclampsia than initially proposed.
publishDate 2020
dc.date.none.fl_str_mv 2020
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10366/154763
url http://hdl.handle.net/10366/154763
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv SAF2010-15881
SAF2013-45784-R
PI16/00460
201920E022
dc.rights.none.fl_str_mv Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:GREDOS. Repositorio Institucional de la Universidad de Salamanca
instname:Universidad de Salamanca (USAL)
instname_str Universidad de Salamanca (USAL)
reponame_str GREDOS. Repositorio Institucional de la Universidad de Salamanca
collection GREDOS. Repositorio Institucional de la Universidad de Salamanca
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869415599476572160
score 15,301603

Similar Items