Balanced levels of nerve growth factor are required for normal pregnancy progression

Autores
Frank, Pierre; Barrientos, Gabriela Laura; Tirado González, Irene; Cohen, Marie; Moschansky, Petra; Peters, Eva M.; Klapp, Burghard F.; Rose, Matthias; Tometten, Mareike; Blois, Sandra M.
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Nerve growth factor (NGF), the first identified member of the family of neurotrophins, is thought to play a critical role in the initiation of the decidual response in stress-challenged pregnant mice. However, the contribution of this pathway to physiological events during the establishment and maintenance of pregnancy remains largely elusive. Using NGF depletion and supplementation strategies alternatively, in this study, we demonstrated that a successful pregnancy is sensitive to disturbances in NGF levels in mice. Treatment with NGF further boosted fetal loss rates in the high-abortion rate CBA/J x DBA/2J mouse model by amplifying a local inflammatory response through recruitment of NGF-expressing immune cells, increased decidual innervation with substance P+ nerve fibres and a Th1 cytokine shift. Similarly, treatment with a NGF-neutralising antibody in BALB/c-mated CBA/J mice, a normal-pregnancy model, also induced abortions associated with increased infiltration of tropomyosin kinase receptor A-expressing NK cells to the decidua. Importantly, in neither of the models, pregnancy loss was associated with defective ovarian function, angiogenesis or placental development. We further demonstrated that spontaneous abortion in humans is associated with up-regulated synthesis and an aberrant distribution of NGF in placental tissue. Thus, a local threshold of NGF expression seems to be necessary to ensure maternal tolerance in healthy pregnancies, but when surpassed may result in fetal rejection due to exacerbated inflammation.
Fil: Frank, Pierre. Medicine University of Berlin; Alemania
Fil: Barrientos, Gabriela Laura. Medicine University of Berlin; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Tirado González, Irene. Medicine University of Berlin; Alemania
Fil: Cohen, Marie. Universidad de Ginebra; Suiza
Fil: Moschansky, Petra. Medicine University of Berlin; Alemania
Fil: Peters, Eva M.. Medicine University of Berlin; Alemania. University Giessen; Alemania
Fil: Klapp, Burghard F.. Medicine University of Berlin; Alemania
Fil: Rose, Matthias. Medicine University of Berlin; Alemania
Fil: Tometten, Mareike. Universitat Duisburg - Essen; Alemania
Fil: Blois, Sandra M.. Medicine University of Berlin; Alemania
Materia
Nerve growth factor
Pregnancy
Spontaneous abortion
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/35958

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spelling Balanced levels of nerve growth factor are required for normal pregnancy progressionFrank, PierreBarrientos, Gabriela LauraTirado González, IreneCohen, MarieMoschansky, PetraPeters, Eva M.Klapp, Burghard F.Rose, MatthiasTometten, MareikeBlois, Sandra M.Nerve growth factorPregnancySpontaneous abortionhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Nerve growth factor (NGF), the first identified member of the family of neurotrophins, is thought to play a critical role in the initiation of the decidual response in stress-challenged pregnant mice. However, the contribution of this pathway to physiological events during the establishment and maintenance of pregnancy remains largely elusive. Using NGF depletion and supplementation strategies alternatively, in this study, we demonstrated that a successful pregnancy is sensitive to disturbances in NGF levels in mice. Treatment with NGF further boosted fetal loss rates in the high-abortion rate CBA/J x DBA/2J mouse model by amplifying a local inflammatory response through recruitment of NGF-expressing immune cells, increased decidual innervation with substance P+ nerve fibres and a Th1 cytokine shift. Similarly, treatment with a NGF-neutralising antibody in BALB/c-mated CBA/J mice, a normal-pregnancy model, also induced abortions associated with increased infiltration of tropomyosin kinase receptor A-expressing NK cells to the decidua. Importantly, in neither of the models, pregnancy loss was associated with defective ovarian function, angiogenesis or placental development. We further demonstrated that spontaneous abortion in humans is associated with up-regulated synthesis and an aberrant distribution of NGF in placental tissue. Thus, a local threshold of NGF expression seems to be necessary to ensure maternal tolerance in healthy pregnancies, but when surpassed may result in fetal rejection due to exacerbated inflammation.Fil: Frank, Pierre. Medicine University of Berlin; AlemaniaFil: Barrientos, Gabriela Laura. Medicine University of Berlin; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Tirado González, Irene. Medicine University of Berlin; AlemaniaFil: Cohen, Marie. Universidad de Ginebra; SuizaFil: Moschansky, Petra. Medicine University of Berlin; AlemaniaFil: Peters, Eva M.. Medicine University of Berlin; Alemania. University Giessen; AlemaniaFil: Klapp, Burghard F.. Medicine University of Berlin; AlemaniaFil: Rose, Matthias. Medicine University of Berlin; AlemaniaFil: Tometten, Mareike. Universitat Duisburg - Essen; AlemaniaFil: Blois, Sandra M.. Medicine University of Berlin; AlemaniaBioScientifica2014-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/35958Frank, Pierre; Barrientos, Gabriela Laura; Tirado González, Irene; Cohen, Marie; Moschansky, Petra; et al.; Balanced levels of nerve growth factor are required for normal pregnancy progression; BioScientifica; Reproduction; 148; 2; 8-2014; 179-1891470-16261741-7899CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1530/REP-14-0112info:eu-repo/semantics/altIdentifier/url/http://www.reproduction-online.org/content/148/2/179info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:03:31Zoai:ri.conicet.gov.ar:11336/35958instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:03:31.479CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Balanced levels of nerve growth factor are required for normal pregnancy progression
title Balanced levels of nerve growth factor are required for normal pregnancy progression
spellingShingle Balanced levels of nerve growth factor are required for normal pregnancy progression
Frank, Pierre
Nerve growth factor
Pregnancy
Spontaneous abortion
title_short Balanced levels of nerve growth factor are required for normal pregnancy progression
title_full Balanced levels of nerve growth factor are required for normal pregnancy progression
title_fullStr Balanced levels of nerve growth factor are required for normal pregnancy progression
title_full_unstemmed Balanced levels of nerve growth factor are required for normal pregnancy progression
title_sort Balanced levels of nerve growth factor are required for normal pregnancy progression
dc.creator.none.fl_str_mv Frank, Pierre
Barrientos, Gabriela Laura
Tirado González, Irene
Cohen, Marie
Moschansky, Petra
Peters, Eva M.
Klapp, Burghard F.
Rose, Matthias
Tometten, Mareike
Blois, Sandra M.
author Frank, Pierre
author_facet Frank, Pierre
Barrientos, Gabriela Laura
Tirado González, Irene
Cohen, Marie
Moschansky, Petra
Peters, Eva M.
Klapp, Burghard F.
Rose, Matthias
Tometten, Mareike
Blois, Sandra M.
author_role author
author2 Barrientos, Gabriela Laura
Tirado González, Irene
Cohen, Marie
Moschansky, Petra
Peters, Eva M.
Klapp, Burghard F.
Rose, Matthias
Tometten, Mareike
Blois, Sandra M.
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Nerve growth factor
Pregnancy
Spontaneous abortion
topic Nerve growth factor
Pregnancy
Spontaneous abortion
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Nerve growth factor (NGF), the first identified member of the family of neurotrophins, is thought to play a critical role in the initiation of the decidual response in stress-challenged pregnant mice. However, the contribution of this pathway to physiological events during the establishment and maintenance of pregnancy remains largely elusive. Using NGF depletion and supplementation strategies alternatively, in this study, we demonstrated that a successful pregnancy is sensitive to disturbances in NGF levels in mice. Treatment with NGF further boosted fetal loss rates in the high-abortion rate CBA/J x DBA/2J mouse model by amplifying a local inflammatory response through recruitment of NGF-expressing immune cells, increased decidual innervation with substance P+ nerve fibres and a Th1 cytokine shift. Similarly, treatment with a NGF-neutralising antibody in BALB/c-mated CBA/J mice, a normal-pregnancy model, also induced abortions associated with increased infiltration of tropomyosin kinase receptor A-expressing NK cells to the decidua. Importantly, in neither of the models, pregnancy loss was associated with defective ovarian function, angiogenesis or placental development. We further demonstrated that spontaneous abortion in humans is associated with up-regulated synthesis and an aberrant distribution of NGF in placental tissue. Thus, a local threshold of NGF expression seems to be necessary to ensure maternal tolerance in healthy pregnancies, but when surpassed may result in fetal rejection due to exacerbated inflammation.
Fil: Frank, Pierre. Medicine University of Berlin; Alemania
Fil: Barrientos, Gabriela Laura. Medicine University of Berlin; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Tirado González, Irene. Medicine University of Berlin; Alemania
Fil: Cohen, Marie. Universidad de Ginebra; Suiza
Fil: Moschansky, Petra. Medicine University of Berlin; Alemania
Fil: Peters, Eva M.. Medicine University of Berlin; Alemania. University Giessen; Alemania
Fil: Klapp, Burghard F.. Medicine University of Berlin; Alemania
Fil: Rose, Matthias. Medicine University of Berlin; Alemania
Fil: Tometten, Mareike. Universitat Duisburg - Essen; Alemania
Fil: Blois, Sandra M.. Medicine University of Berlin; Alemania
description Nerve growth factor (NGF), the first identified member of the family of neurotrophins, is thought to play a critical role in the initiation of the decidual response in stress-challenged pregnant mice. However, the contribution of this pathway to physiological events during the establishment and maintenance of pregnancy remains largely elusive. Using NGF depletion and supplementation strategies alternatively, in this study, we demonstrated that a successful pregnancy is sensitive to disturbances in NGF levels in mice. Treatment with NGF further boosted fetal loss rates in the high-abortion rate CBA/J x DBA/2J mouse model by amplifying a local inflammatory response through recruitment of NGF-expressing immune cells, increased decidual innervation with substance P+ nerve fibres and a Th1 cytokine shift. Similarly, treatment with a NGF-neutralising antibody in BALB/c-mated CBA/J mice, a normal-pregnancy model, also induced abortions associated with increased infiltration of tropomyosin kinase receptor A-expressing NK cells to the decidua. Importantly, in neither of the models, pregnancy loss was associated with defective ovarian function, angiogenesis or placental development. We further demonstrated that spontaneous abortion in humans is associated with up-regulated synthesis and an aberrant distribution of NGF in placental tissue. Thus, a local threshold of NGF expression seems to be necessary to ensure maternal tolerance in healthy pregnancies, but when surpassed may result in fetal rejection due to exacerbated inflammation.
publishDate 2014
dc.date.none.fl_str_mv 2014-08
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/35958
Frank, Pierre; Barrientos, Gabriela Laura; Tirado González, Irene; Cohen, Marie; Moschansky, Petra; et al.; Balanced levels of nerve growth factor are required for normal pregnancy progression; BioScientifica; Reproduction; 148; 2; 8-2014; 179-189
1470-1626
1741-7899
CONICET Digital
CONICET
url http://hdl.handle.net/11336/35958
identifier_str_mv Frank, Pierre; Barrientos, Gabriela Laura; Tirado González, Irene; Cohen, Marie; Moschansky, Petra; et al.; Balanced levels of nerve growth factor are required for normal pregnancy progression; BioScientifica; Reproduction; 148; 2; 8-2014; 179-189
1470-1626
1741-7899
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1530/REP-14-0112
info:eu-repo/semantics/altIdentifier/url/http://www.reproduction-online.org/content/148/2/179
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv BioScientifica
publisher.none.fl_str_mv BioScientifica
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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