Absence of Heme Oxygenase-1 Affects Trophoblastic Spheroid Implantation and Provokes Dysregulation of Stress and Angiogenesis Gene Expression in the Uterus

Autores
Zenclussen, Maria Laura; Ulrich, Sina; Bauer, Mario; Fink, Beate; Zenclussen, Ana Claudia; Schumacher, Anne; Meyer, Nicole
Año de publicación
2024
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The enzyme heme oxygenase-1 (HO-1) is pivotal in reproductive processes, particularly in placental and vascular development. This study investigated the role of HO-1 and its byproduct, carbon monoxide (CO), in trophoblastic spheroid implantation. In order to deepen our understanding of the role of HO-1 during implantation, we conducted in vivo experiments on virgin and pregnant mice, aiming to unravel the cellular and molecular mechanisms. Using siRNA, HO-1 was knocked down in JEG-3 and BeWo cells and trophoblastic spheroids were generated with or without CO treatment. Adhesion assays were performed after transferring the spheroids to RL-95 endometrial epithelial cell layers. Additionally, angiogenesis, stress, and toxicity RT2-Profiler™ PCR SuperArray and PCR analyses were performed in uterine murine samples. HO-1 knockdown by siRNA impeded implantation in the 3D culture model, but this effect could be reversed by CO. Uteruses from virgin Hmox1−/− females exhibited altered expression of angiogenesis and stress markers. Furthermore, there was a distinct expression pattern of cytokines and chemokines in uteruses from gestation day 14 in Hmox1−/− females compared to Hmox1+/+ females. This study strongly supports the essential role of HO-1 during implantation. Moreover, CO appears to have the potential to compensate for the lack of HO-1 during the spheroid attachment process. The absence of HO-1 results in dysregulation of angiogenesis and stress-related genes in the uterus, possibly contributing to implantation failure.
Fil: Zenclussen, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Salud y Ambiente del Litoral. Universidad Nacional del Litoral. Instituto de Salud y Ambiente del Litoral; Argentina
Fil: Ulrich, Sina. Otto-von-Guericke University Magdeburg; Alemania
Fil: Bauer, Mario. Helmholtz Centre for Environmental Research; Alemania
Fil: Fink, Beate. Helmholtz Centre for Environmental Research; Alemania
Fil: Zenclussen, Ana Claudia. Helmholtz Centre for Environmental Research; Alemania. Otto-von-Guericke University Magdeburg; Alemania
Fil: Schumacher, Anne. Otto-von-Guericke University Magdeburg; Alemania. Helmholtz Centre for Environmental Research; Alemania
Fil: Meyer, Nicole. Otto-von-Guericke University Magdeburg; Alemania. Helmholtz Centre for Environmental Research; Alemania
Materia
HEME OXYGENASE-1
IMPLANTATION
PREGNANCY
ANGIOGENESIS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/257570
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/257570
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Absence of Heme Oxygenase-1 Affects Trophoblastic Spheroid Implantation and Provokes Dysregulation of Stress and Angiogenesis Gene Expression in the UterusZenclussen, Maria LauraUlrich, SinaBauer, MarioFink, BeateZenclussen, Ana ClaudiaSchumacher, AnneMeyer, NicoleHEME OXYGENASE-1IMPLANTATIONPREGNANCYANGIOGENESIShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The enzyme heme oxygenase-1 (HO-1) is pivotal in reproductive processes, particularly in placental and vascular development. This study investigated the role of HO-1 and its byproduct, carbon monoxide (CO), in trophoblastic spheroid implantation. In order to deepen our understanding of the role of HO-1 during implantation, we conducted in vivo experiments on virgin and pregnant mice, aiming to unravel the cellular and molecular mechanisms. Using siRNA, HO-1 was knocked down in JEG-3 and BeWo cells and trophoblastic spheroids were generated with or without CO treatment. Adhesion assays were performed after transferring the spheroids to RL-95 endometrial epithelial cell layers. Additionally, angiogenesis, stress, and toxicity RT2-Profiler™ PCR SuperArray and PCR analyses were performed in uterine murine samples. HO-1 knockdown by siRNA impeded implantation in the 3D culture model, but this effect could be reversed by CO. Uteruses from virgin Hmox1−/− females exhibited altered expression of angiogenesis and stress markers. Furthermore, there was a distinct expression pattern of cytokines and chemokines in uteruses from gestation day 14 in Hmox1−/− females compared to Hmox1+/+ females. This study strongly supports the essential role of HO-1 during implantation. Moreover, CO appears to have the potential to compensate for the lack of HO-1 during the spheroid attachment process. The absence of HO-1 results in dysregulation of angiogenesis and stress-related genes in the uterus, possibly contributing to implantation failure.Fil: Zenclussen, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Salud y Ambiente del Litoral. Universidad Nacional del Litoral. Instituto de Salud y Ambiente del Litoral; ArgentinaFil: Ulrich, Sina. Otto-von-Guericke University Magdeburg; AlemaniaFil: Bauer, Mario. Helmholtz Centre for Environmental Research; AlemaniaFil: Fink, Beate. Helmholtz Centre for Environmental Research; AlemaniaFil: Zenclussen, Ana Claudia. Helmholtz Centre for Environmental Research; Alemania. Otto-von-Guericke University Magdeburg; AlemaniaFil: Schumacher, Anne. Otto-von-Guericke University Magdeburg; Alemania. Helmholtz Centre for Environmental Research; AlemaniaFil: Meyer, Nicole. Otto-von-Guericke University Magdeburg; Alemania. Helmholtz Centre for Environmental Research; AlemaniaMDPI2024-02info: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/11336/257570Zenclussen, Maria Laura; Ulrich, Sina; Bauer, Mario; Fink, Beate; Zenclussen, Ana Claudia; et al.; Absence of Heme Oxygenase-1 Affects Trophoblastic Spheroid Implantation and Provokes Dysregulation of Stress and Angiogenesis Gene Expression in the Uterus; MDPI; Cells; 13; 5; 2-2024; 1-132073-44092073-4409CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2073-4409/13/5/376info:eu-repo/semantics/altIdentifier/doi/10.3390/cells13050376info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:00:00Zoai:ri.conicet.gov.ar:11336/257570instacron: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:34982025-09-10 13:00:00.704CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Absence of Heme Oxygenase-1 Affects Trophoblastic Spheroid Implantation and Provokes Dysregulation of Stress and Angiogenesis Gene Expression in the Uterus
title Absence of Heme Oxygenase-1 Affects Trophoblastic Spheroid Implantation and Provokes Dysregulation of Stress and Angiogenesis Gene Expression in the Uterus
spellingShingle Absence of Heme Oxygenase-1 Affects Trophoblastic Spheroid Implantation and Provokes Dysregulation of Stress and Angiogenesis Gene Expression in the Uterus
Zenclussen, Maria Laura
HEME OXYGENASE-1
IMPLANTATION
PREGNANCY
ANGIOGENESIS
title_short Absence of Heme Oxygenase-1 Affects Trophoblastic Spheroid Implantation and Provokes Dysregulation of Stress and Angiogenesis Gene Expression in the Uterus
title_full Absence of Heme Oxygenase-1 Affects Trophoblastic Spheroid Implantation and Provokes Dysregulation of Stress and Angiogenesis Gene Expression in the Uterus
title_fullStr Absence of Heme Oxygenase-1 Affects Trophoblastic Spheroid Implantation and Provokes Dysregulation of Stress and Angiogenesis Gene Expression in the Uterus
title_full_unstemmed Absence of Heme Oxygenase-1 Affects Trophoblastic Spheroid Implantation and Provokes Dysregulation of Stress and Angiogenesis Gene Expression in the Uterus
title_sort Absence of Heme Oxygenase-1 Affects Trophoblastic Spheroid Implantation and Provokes Dysregulation of Stress and Angiogenesis Gene Expression in the Uterus
dc.creator.none.fl_str_mv Zenclussen, Maria Laura
Ulrich, Sina
Bauer, Mario
Fink, Beate
Zenclussen, Ana Claudia
Schumacher, Anne
Meyer, Nicole
author Zenclussen, Maria Laura
author_facet Zenclussen, Maria Laura
Ulrich, Sina
Bauer, Mario
Fink, Beate
Zenclussen, Ana Claudia
Schumacher, Anne
Meyer, Nicole
author_role author
author2 Ulrich, Sina
Bauer, Mario
Fink, Beate
Zenclussen, Ana Claudia
Schumacher, Anne
Meyer, Nicole
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv HEME OXYGENASE-1
IMPLANTATION
PREGNANCY
ANGIOGENESIS
topic HEME OXYGENASE-1
IMPLANTATION
PREGNANCY
ANGIOGENESIS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The enzyme heme oxygenase-1 (HO-1) is pivotal in reproductive processes, particularly in placental and vascular development. This study investigated the role of HO-1 and its byproduct, carbon monoxide (CO), in trophoblastic spheroid implantation. In order to deepen our understanding of the role of HO-1 during implantation, we conducted in vivo experiments on virgin and pregnant mice, aiming to unravel the cellular and molecular mechanisms. Using siRNA, HO-1 was knocked down in JEG-3 and BeWo cells and trophoblastic spheroids were generated with or without CO treatment. Adhesion assays were performed after transferring the spheroids to RL-95 endometrial epithelial cell layers. Additionally, angiogenesis, stress, and toxicity RT2-Profiler™ PCR SuperArray and PCR analyses were performed in uterine murine samples. HO-1 knockdown by siRNA impeded implantation in the 3D culture model, but this effect could be reversed by CO. Uteruses from virgin Hmox1−/− females exhibited altered expression of angiogenesis and stress markers. Furthermore, there was a distinct expression pattern of cytokines and chemokines in uteruses from gestation day 14 in Hmox1−/− females compared to Hmox1+/+ females. This study strongly supports the essential role of HO-1 during implantation. Moreover, CO appears to have the potential to compensate for the lack of HO-1 during the spheroid attachment process. The absence of HO-1 results in dysregulation of angiogenesis and stress-related genes in the uterus, possibly contributing to implantation failure.
Fil: Zenclussen, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Salud y Ambiente del Litoral. Universidad Nacional del Litoral. Instituto de Salud y Ambiente del Litoral; Argentina
Fil: Ulrich, Sina. Otto-von-Guericke University Magdeburg; Alemania
Fil: Bauer, Mario. Helmholtz Centre for Environmental Research; Alemania
Fil: Fink, Beate. Helmholtz Centre for Environmental Research; Alemania
Fil: Zenclussen, Ana Claudia. Helmholtz Centre for Environmental Research; Alemania. Otto-von-Guericke University Magdeburg; Alemania
Fil: Schumacher, Anne. Otto-von-Guericke University Magdeburg; Alemania. Helmholtz Centre for Environmental Research; Alemania
Fil: Meyer, Nicole. Otto-von-Guericke University Magdeburg; Alemania. Helmholtz Centre for Environmental Research; Alemania
description The enzyme heme oxygenase-1 (HO-1) is pivotal in reproductive processes, particularly in placental and vascular development. This study investigated the role of HO-1 and its byproduct, carbon monoxide (CO), in trophoblastic spheroid implantation. In order to deepen our understanding of the role of HO-1 during implantation, we conducted in vivo experiments on virgin and pregnant mice, aiming to unravel the cellular and molecular mechanisms. Using siRNA, HO-1 was knocked down in JEG-3 and BeWo cells and trophoblastic spheroids were generated with or without CO treatment. Adhesion assays were performed after transferring the spheroids to RL-95 endometrial epithelial cell layers. Additionally, angiogenesis, stress, and toxicity RT2-Profiler™ PCR SuperArray and PCR analyses were performed in uterine murine samples. HO-1 knockdown by siRNA impeded implantation in the 3D culture model, but this effect could be reversed by CO. Uteruses from virgin Hmox1−/− females exhibited altered expression of angiogenesis and stress markers. Furthermore, there was a distinct expression pattern of cytokines and chemokines in uteruses from gestation day 14 in Hmox1−/− females compared to Hmox1+/+ females. This study strongly supports the essential role of HO-1 during implantation. Moreover, CO appears to have the potential to compensate for the lack of HO-1 during the spheroid attachment process. The absence of HO-1 results in dysregulation of angiogenesis and stress-related genes in the uterus, possibly contributing to implantation failure.
publishDate 2024
dc.date.none.fl_str_mv 2024-02
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/11336/257570
Zenclussen, Maria Laura; Ulrich, Sina; Bauer, Mario; Fink, Beate; Zenclussen, Ana Claudia; et al.; Absence of Heme Oxygenase-1 Affects Trophoblastic Spheroid Implantation and Provokes Dysregulation of Stress and Angiogenesis Gene Expression in the Uterus; MDPI; Cells; 13; 5; 2-2024; 1-13
2073-4409
2073-4409
CONICET Digital
CONICET
url http://hdl.handle.net/11336/257570
identifier_str_mv Zenclussen, Maria Laura; Ulrich, Sina; Bauer, Mario; Fink, Beate; Zenclussen, Ana Claudia; et al.; Absence of Heme Oxygenase-1 Affects Trophoblastic Spheroid Implantation and Provokes Dysregulation of Stress and Angiogenesis Gene Expression in the Uterus; MDPI; Cells; 13; 5; 2-2024; 1-13
2073-4409
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2073-4409/13/5/376
info:eu-repo/semantics/altIdentifier/doi/10.3390/cells13050376
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
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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score 12.48226

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