Perinatal Exposure to Glyphosate or a Commercial Formulation Alters Uterine Mechanistic Pathways Associated with Implantation Failure in Rats

Autores
Almiron, Ailin; Lorenz, Virginia; Varayoud, Jorgelina Guadalupe; Durando, Milena de Lourdes; Milesi, Maria Mercedes
Año de publicación
2024
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Perinatal exposure to a glyphosate-based herbicide (GBH) or its active ingredient, glyphosate (Gly), has been demonstrated to increase implantation failure in rats. This study investigates potential mechanisms of action, analyzing uterine preparation towards the receptive state. Pregnant Wistar rats (F0) were treated orally with GBH or Gly (3.8 and 3.9 mg Gly/kg/day, respectively) from gestational day (GD) 9 until weaning. Adult F1 females became pregnant and uterine samples were collected on GD5 (preimplantation period). Histomorphological uterine parameters were assessed. Immunohistochemistry was applied to evaluate cell proliferation and protein expression of estrogen receptors (ERα and ERβ), cell cycle regulators (PTEN, cyclin G1, p27, and IGF1R-α), and the Wnt5a/β-catenin/FOXA2/Lif pathway. Both GBH and Gly females showed increased stromal proliferation, associated with a high expression of ERs. Dysregulation of PTEN and cyclin G1 was also observed in the Gly group. Reduced gland number was observed in both groups, along with decreased expression of Wnt5a/β-catenin/FOXA2/Lif pathway in the glandular epithelium. Overall, GBH and Gly perinatal exposure disrupted intrinsic uterine pathways involved in endometrial proliferation and glandular function, providing a plausible mechanism for glyphosate-induced implantation failure by compromising uterine receptivity. Similar effects between GBH and Gly suggest the active principle mainly drives the adverse outcomes.
Fil: Almiron, Ailin. 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: Lorenz, Virginia. 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: Varayoud, Jorgelina Guadalupe. 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: Durando, Milena de Lourdes. 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: Milesi, Maria Mercedes. 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
Materia
GLYPHOSATE
IMPLANTATION FAILURE
ENDOMETRIAL RECEPTIVITY
PROLIFERATION
GLANDULAR FUNCTION
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:11336/264459
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/264459
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Perinatal Exposure to Glyphosate or a Commercial Formulation Alters Uterine Mechanistic Pathways Associated with Implantation Failure in RatsAlmiron, AilinLorenz, VirginiaVarayoud, Jorgelina GuadalupeDurando, Milena de LourdesMilesi, Maria MercedesGLYPHOSATEIMPLANTATION FAILUREENDOMETRIAL RECEPTIVITYPROLIFERATIONGLANDULAR FUNCTIONhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Perinatal exposure to a glyphosate-based herbicide (GBH) or its active ingredient, glyphosate (Gly), has been demonstrated to increase implantation failure in rats. This study investigates potential mechanisms of action, analyzing uterine preparation towards the receptive state. Pregnant Wistar rats (F0) were treated orally with GBH or Gly (3.8 and 3.9 mg Gly/kg/day, respectively) from gestational day (GD) 9 until weaning. Adult F1 females became pregnant and uterine samples were collected on GD5 (preimplantation period). Histomorphological uterine parameters were assessed. Immunohistochemistry was applied to evaluate cell proliferation and protein expression of estrogen receptors (ERα and ERβ), cell cycle regulators (PTEN, cyclin G1, p27, and IGF1R-α), and the Wnt5a/β-catenin/FOXA2/Lif pathway. Both GBH and Gly females showed increased stromal proliferation, associated with a high expression of ERs. Dysregulation of PTEN and cyclin G1 was also observed in the Gly group. Reduced gland number was observed in both groups, along with decreased expression of Wnt5a/β-catenin/FOXA2/Lif pathway in the glandular epithelium. Overall, GBH and Gly perinatal exposure disrupted intrinsic uterine pathways involved in endometrial proliferation and glandular function, providing a plausible mechanism for glyphosate-induced implantation failure by compromising uterine receptivity. Similar effects between GBH and Gly suggest the active principle mainly drives the adverse outcomes.Fil: Almiron, Ailin. 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: Lorenz, Virginia. 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: Varayoud, Jorgelina Guadalupe. 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: Durando, Milena de Lourdes. 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: Milesi, Maria Mercedes. 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; ArgentinaMDPI2024-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/264459Almiron, Ailin; Lorenz, Virginia; Varayoud, Jorgelina Guadalupe; Durando, Milena de Lourdes; Milesi, Maria Mercedes; Perinatal Exposure to Glyphosate or a Commercial Formulation Alters Uterine Mechanistic Pathways Associated with Implantation Failure in Rats; MDPI; Toxics; 12; 8; 8-2024; 1-182305-6304CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2305-6304/12/8/590info:eu-repo/semantics/altIdentifier/doi/10.3390/toxics12080590info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:23:21Zoai:ri.conicet.gov.ar:11336/264459instacron: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:34982025-10-22 11:23:21.385CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Perinatal Exposure to Glyphosate or a Commercial Formulation Alters Uterine Mechanistic Pathways Associated with Implantation Failure in Rats
title Perinatal Exposure to Glyphosate or a Commercial Formulation Alters Uterine Mechanistic Pathways Associated with Implantation Failure in Rats
spellingShingle Perinatal Exposure to Glyphosate or a Commercial Formulation Alters Uterine Mechanistic Pathways Associated with Implantation Failure in Rats
Almiron, Ailin
GLYPHOSATE
IMPLANTATION FAILURE
ENDOMETRIAL RECEPTIVITY
PROLIFERATION
GLANDULAR FUNCTION
title_short Perinatal Exposure to Glyphosate or a Commercial Formulation Alters Uterine Mechanistic Pathways Associated with Implantation Failure in Rats
title_full Perinatal Exposure to Glyphosate or a Commercial Formulation Alters Uterine Mechanistic Pathways Associated with Implantation Failure in Rats
title_fullStr Perinatal Exposure to Glyphosate or a Commercial Formulation Alters Uterine Mechanistic Pathways Associated with Implantation Failure in Rats
title_full_unstemmed Perinatal Exposure to Glyphosate or a Commercial Formulation Alters Uterine Mechanistic Pathways Associated with Implantation Failure in Rats
title_sort Perinatal Exposure to Glyphosate or a Commercial Formulation Alters Uterine Mechanistic Pathways Associated with Implantation Failure in Rats
dc.creator.none.fl_str_mv Almiron, Ailin
Lorenz, Virginia
Varayoud, Jorgelina Guadalupe
Durando, Milena de Lourdes
Milesi, Maria Mercedes
author Almiron, Ailin
author_facet Almiron, Ailin
Lorenz, Virginia
Varayoud, Jorgelina Guadalupe
Durando, Milena de Lourdes
Milesi, Maria Mercedes
author_role author
author2 Lorenz, Virginia
Varayoud, Jorgelina Guadalupe
Durando, Milena de Lourdes
Milesi, Maria Mercedes
author2_role author
author
author
author
dc.subject.none.fl_str_mv GLYPHOSATE
IMPLANTATION FAILURE
ENDOMETRIAL RECEPTIVITY
PROLIFERATION
GLANDULAR FUNCTION
topic GLYPHOSATE
IMPLANTATION FAILURE
ENDOMETRIAL RECEPTIVITY
PROLIFERATION
GLANDULAR FUNCTION
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Perinatal exposure to a glyphosate-based herbicide (GBH) or its active ingredient, glyphosate (Gly), has been demonstrated to increase implantation failure in rats. This study investigates potential mechanisms of action, analyzing uterine preparation towards the receptive state. Pregnant Wistar rats (F0) were treated orally with GBH or Gly (3.8 and 3.9 mg Gly/kg/day, respectively) from gestational day (GD) 9 until weaning. Adult F1 females became pregnant and uterine samples were collected on GD5 (preimplantation period). Histomorphological uterine parameters were assessed. Immunohistochemistry was applied to evaluate cell proliferation and protein expression of estrogen receptors (ERα and ERβ), cell cycle regulators (PTEN, cyclin G1, p27, and IGF1R-α), and the Wnt5a/β-catenin/FOXA2/Lif pathway. Both GBH and Gly females showed increased stromal proliferation, associated with a high expression of ERs. Dysregulation of PTEN and cyclin G1 was also observed in the Gly group. Reduced gland number was observed in both groups, along with decreased expression of Wnt5a/β-catenin/FOXA2/Lif pathway in the glandular epithelium. Overall, GBH and Gly perinatal exposure disrupted intrinsic uterine pathways involved in endometrial proliferation and glandular function, providing a plausible mechanism for glyphosate-induced implantation failure by compromising uterine receptivity. Similar effects between GBH and Gly suggest the active principle mainly drives the adverse outcomes.
Fil: Almiron, Ailin. 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: Lorenz, Virginia. 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: Varayoud, Jorgelina Guadalupe. 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: Durando, Milena de Lourdes. 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: Milesi, Maria Mercedes. 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
description Perinatal exposure to a glyphosate-based herbicide (GBH) or its active ingredient, glyphosate (Gly), has been demonstrated to increase implantation failure in rats. This study investigates potential mechanisms of action, analyzing uterine preparation towards the receptive state. Pregnant Wistar rats (F0) were treated orally with GBH or Gly (3.8 and 3.9 mg Gly/kg/day, respectively) from gestational day (GD) 9 until weaning. Adult F1 females became pregnant and uterine samples were collected on GD5 (preimplantation period). Histomorphological uterine parameters were assessed. Immunohistochemistry was applied to evaluate cell proliferation and protein expression of estrogen receptors (ERα and ERβ), cell cycle regulators (PTEN, cyclin G1, p27, and IGF1R-α), and the Wnt5a/β-catenin/FOXA2/Lif pathway. Both GBH and Gly females showed increased stromal proliferation, associated with a high expression of ERs. Dysregulation of PTEN and cyclin G1 was also observed in the Gly group. Reduced gland number was observed in both groups, along with decreased expression of Wnt5a/β-catenin/FOXA2/Lif pathway in the glandular epithelium. Overall, GBH and Gly perinatal exposure disrupted intrinsic uterine pathways involved in endometrial proliferation and glandular function, providing a plausible mechanism for glyphosate-induced implantation failure by compromising uterine receptivity. Similar effects between GBH and Gly suggest the active principle mainly drives the adverse outcomes.
publishDate 2024
dc.date.none.fl_str_mv 2024-08
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/11336/264459
Almiron, Ailin; Lorenz, Virginia; Varayoud, Jorgelina Guadalupe; Durando, Milena de Lourdes; Milesi, Maria Mercedes; Perinatal Exposure to Glyphosate or a Commercial Formulation Alters Uterine Mechanistic Pathways Associated with Implantation Failure in Rats; MDPI; Toxics; 12; 8; 8-2024; 1-18
2305-6304
CONICET Digital
CONICET
url http://hdl.handle.net/11336/264459
identifier_str_mv Almiron, Ailin; Lorenz, Virginia; Varayoud, Jorgelina Guadalupe; Durando, Milena de Lourdes; Milesi, Maria Mercedes; Perinatal Exposure to Glyphosate or a Commercial Formulation Alters Uterine Mechanistic Pathways Associated with Implantation Failure in Rats; MDPI; Toxics; 12; 8; 8-2024; 1-18
2305-6304
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/2305-6304/12/8/590
info:eu-repo/semantics/altIdentifier/doi/10.3390/toxics12080590
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
application/pdf
application/pdf
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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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