Glyphosate-based herbicides produce teratogenic effects on vertebrates by impairing retinoic acid signaling

Autores
Paganelli, Alejandra Raquel; Gnazzo, Victoria; Acosta, Helena; Lopez, Silvia Liliana; Carrasco, Andres Eduardo
Año de publicación
2010
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The broad spectrum herbicide glyphosate is widely used in agriculture worldwide. There has been ongoing controversy regarding the possible adverse effects of glyphosate on the environment and on human health. Reports of neural defects and craniofacial malformations from regions where glyphosate-based herbicides (GBH) are used led us to undertake an embryological approach to explore the effects of low doses of glyphosate in development. Xenopus laevis embryos were incubated with 1/5000 dilutions of a commercial GBH. The treated embryos were highly abnormal with marked alterations in cephalic and neural crest development and shortening of the anterior posterior (A-P) axis. Alterations on neural crest markers were later correlated with deformities in the cranial cartilages at tadpole stages. Embryos injected with pure glyphosate showed very similar phenotypes. Moreover, GBH produced similar effects in chicken embryos, showing a gradual loss of rhombomere domains, reduction of the optic vesicles, and microcephaly. This suggests that glyphosate itself was responsible for the phenotypes observed, rather than a surfactant or other component of the commercial formulation. A reporter gene assay revealed that GBH treatment increased endogenous retinoic acid (RA) activity in Xenopus embryos and cotreatment with a RA antagonist rescued the teratogenic effects of the GBH. Therefore, we conclude that the phenotypes produced by GBH are mainly a consequence of the increase of endogenous retinoid activity. This is consistent with the decrease of Sonic hedgehog (Shh) signaling from the embryonic dorsal midline, with the inhibition of otx2 expression and with the disruption of cephalic neural crest development. The direct effect of glyphosate on early mechanisms of morphogenesis in vertebrate embryos opens concerns about the clinical findings from human offspring in populations exposed to GBH in agricultural fields.
Fil: Paganelli, Alejandra Raquel. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Gnazzo, Victoria. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Acosta, Helena. Universidad de Buenos Aires. Facultad de Medicina; Argentina
Fil: Lopez, Silvia Liliana. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Carrasco, Andres Eduardo. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
Xenopus
Ra
Shh
Neural Crest
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:11336/67699
Acceder
id CONICETDig_5e59202d4ca809a1c83598f13f962db7
oai_identifier_str oai:ri.conicet.gov.ar:11336/67699
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Glyphosate-based herbicides produce teratogenic effects on vertebrates by impairing retinoic acid signalingPaganelli, Alejandra RaquelGnazzo, VictoriaAcosta, HelenaLopez, Silvia LilianaCarrasco, Andres EduardoXenopusRaShhNeural Cresthttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The broad spectrum herbicide glyphosate is widely used in agriculture worldwide. There has been ongoing controversy regarding the possible adverse effects of glyphosate on the environment and on human health. Reports of neural defects and craniofacial malformations from regions where glyphosate-based herbicides (GBH) are used led us to undertake an embryological approach to explore the effects of low doses of glyphosate in development. Xenopus laevis embryos were incubated with 1/5000 dilutions of a commercial GBH. The treated embryos were highly abnormal with marked alterations in cephalic and neural crest development and shortening of the anterior posterior (A-P) axis. Alterations on neural crest markers were later correlated with deformities in the cranial cartilages at tadpole stages. Embryos injected with pure glyphosate showed very similar phenotypes. Moreover, GBH produced similar effects in chicken embryos, showing a gradual loss of rhombomere domains, reduction of the optic vesicles, and microcephaly. This suggests that glyphosate itself was responsible for the phenotypes observed, rather than a surfactant or other component of the commercial formulation. A reporter gene assay revealed that GBH treatment increased endogenous retinoic acid (RA) activity in Xenopus embryos and cotreatment with a RA antagonist rescued the teratogenic effects of the GBH. Therefore, we conclude that the phenotypes produced by GBH are mainly a consequence of the increase of endogenous retinoid activity. This is consistent with the decrease of Sonic hedgehog (Shh) signaling from the embryonic dorsal midline, with the inhibition of otx2 expression and with the disruption of cephalic neural crest development. The direct effect of glyphosate on early mechanisms of morphogenesis in vertebrate embryos opens concerns about the clinical findings from human offspring in populations exposed to GBH in agricultural fields.Fil: Paganelli, Alejandra Raquel. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gnazzo, Victoria. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Acosta, Helena. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Lopez, Silvia Liliana. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Carrasco, Andres Eduardo. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaAmerican Chemical Society2010-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/67699Paganelli, Alejandra Raquel; Gnazzo, Victoria; Acosta, Helena; Lopez, Silvia Liliana; Carrasco, Andres Eduardo; Glyphosate-based herbicides produce teratogenic effects on vertebrates by impairing retinoic acid signaling; American Chemical Society; Chemical Research In Toxicology (Washington); 23; 10; 10-2010; 1586-15950893-228XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1021/tx1001749info:eu-repo/semantics/altIdentifier/url/https://pubs.acs.org/doi/abs/10.1021/tx1001749info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-11-12T09:59:27Zoai:ri.conicet.gov.ar:11336/67699instacron: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:34982025-11-12 09:59:27.676CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Glyphosate-based herbicides produce teratogenic effects on vertebrates by impairing retinoic acid signaling
title Glyphosate-based herbicides produce teratogenic effects on vertebrates by impairing retinoic acid signaling
spellingShingle Glyphosate-based herbicides produce teratogenic effects on vertebrates by impairing retinoic acid signaling
Paganelli, Alejandra Raquel
Xenopus
Ra
Shh
Neural Crest
title_short Glyphosate-based herbicides produce teratogenic effects on vertebrates by impairing retinoic acid signaling
title_full Glyphosate-based herbicides produce teratogenic effects on vertebrates by impairing retinoic acid signaling
title_fullStr Glyphosate-based herbicides produce teratogenic effects on vertebrates by impairing retinoic acid signaling
title_full_unstemmed Glyphosate-based herbicides produce teratogenic effects on vertebrates by impairing retinoic acid signaling
title_sort Glyphosate-based herbicides produce teratogenic effects on vertebrates by impairing retinoic acid signaling
dc.creator.none.fl_str_mv Paganelli, Alejandra Raquel
Gnazzo, Victoria
Acosta, Helena
Lopez, Silvia Liliana
Carrasco, Andres Eduardo
author Paganelli, Alejandra Raquel
author_facet Paganelli, Alejandra Raquel
Gnazzo, Victoria
Acosta, Helena
Lopez, Silvia Liliana
Carrasco, Andres Eduardo
author_role author
author2 Gnazzo, Victoria
Acosta, Helena
Lopez, Silvia Liliana
Carrasco, Andres Eduardo
author2_role author
author
author
author
dc.subject.none.fl_str_mv Xenopus
Ra
Shh
Neural Crest
topic Xenopus
Ra
Shh
Neural Crest
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 broad spectrum herbicide glyphosate is widely used in agriculture worldwide. There has been ongoing controversy regarding the possible adverse effects of glyphosate on the environment and on human health. Reports of neural defects and craniofacial malformations from regions where glyphosate-based herbicides (GBH) are used led us to undertake an embryological approach to explore the effects of low doses of glyphosate in development. Xenopus laevis embryos were incubated with 1/5000 dilutions of a commercial GBH. The treated embryos were highly abnormal with marked alterations in cephalic and neural crest development and shortening of the anterior posterior (A-P) axis. Alterations on neural crest markers were later correlated with deformities in the cranial cartilages at tadpole stages. Embryos injected with pure glyphosate showed very similar phenotypes. Moreover, GBH produced similar effects in chicken embryos, showing a gradual loss of rhombomere domains, reduction of the optic vesicles, and microcephaly. This suggests that glyphosate itself was responsible for the phenotypes observed, rather than a surfactant or other component of the commercial formulation. A reporter gene assay revealed that GBH treatment increased endogenous retinoic acid (RA) activity in Xenopus embryos and cotreatment with a RA antagonist rescued the teratogenic effects of the GBH. Therefore, we conclude that the phenotypes produced by GBH are mainly a consequence of the increase of endogenous retinoid activity. This is consistent with the decrease of Sonic hedgehog (Shh) signaling from the embryonic dorsal midline, with the inhibition of otx2 expression and with the disruption of cephalic neural crest development. The direct effect of glyphosate on early mechanisms of morphogenesis in vertebrate embryos opens concerns about the clinical findings from human offspring in populations exposed to GBH in agricultural fields.
Fil: Paganelli, Alejandra Raquel. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Gnazzo, Victoria. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Acosta, Helena. Universidad de Buenos Aires. Facultad de Medicina; Argentina
Fil: Lopez, Silvia Liliana. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Carrasco, Andres Eduardo. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description The broad spectrum herbicide glyphosate is widely used in agriculture worldwide. There has been ongoing controversy regarding the possible adverse effects of glyphosate on the environment and on human health. Reports of neural defects and craniofacial malformations from regions where glyphosate-based herbicides (GBH) are used led us to undertake an embryological approach to explore the effects of low doses of glyphosate in development. Xenopus laevis embryos were incubated with 1/5000 dilutions of a commercial GBH. The treated embryos were highly abnormal with marked alterations in cephalic and neural crest development and shortening of the anterior posterior (A-P) axis. Alterations on neural crest markers were later correlated with deformities in the cranial cartilages at tadpole stages. Embryos injected with pure glyphosate showed very similar phenotypes. Moreover, GBH produced similar effects in chicken embryos, showing a gradual loss of rhombomere domains, reduction of the optic vesicles, and microcephaly. This suggests that glyphosate itself was responsible for the phenotypes observed, rather than a surfactant or other component of the commercial formulation. A reporter gene assay revealed that GBH treatment increased endogenous retinoic acid (RA) activity in Xenopus embryos and cotreatment with a RA antagonist rescued the teratogenic effects of the GBH. Therefore, we conclude that the phenotypes produced by GBH are mainly a consequence of the increase of endogenous retinoid activity. This is consistent with the decrease of Sonic hedgehog (Shh) signaling from the embryonic dorsal midline, with the inhibition of otx2 expression and with the disruption of cephalic neural crest development. The direct effect of glyphosate on early mechanisms of morphogenesis in vertebrate embryos opens concerns about the clinical findings from human offspring in populations exposed to GBH in agricultural fields.
publishDate 2010
dc.date.none.fl_str_mv 2010-10
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/11336/67699
Paganelli, Alejandra Raquel; Gnazzo, Victoria; Acosta, Helena; Lopez, Silvia Liliana; Carrasco, Andres Eduardo; Glyphosate-based herbicides produce teratogenic effects on vertebrates by impairing retinoic acid signaling; American Chemical Society; Chemical Research In Toxicology (Washington); 23; 10; 10-2010; 1586-1595
0893-228X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/67699
identifier_str_mv Paganelli, Alejandra Raquel; Gnazzo, Victoria; Acosta, Helena; Lopez, Silvia Liliana; Carrasco, Andres Eduardo; Glyphosate-based herbicides produce teratogenic effects on vertebrates by impairing retinoic acid signaling; American Chemical Society; Chemical Research In Toxicology (Washington); 23; 10; 10-2010; 1586-1595
0893-228X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1021/tx1001749
info:eu-repo/semantics/altIdentifier/url/https://pubs.acs.org/doi/abs/10.1021/tx1001749
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
application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Chemical Society
publisher.none.fl_str_mv American Chemical Society
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
_version_ 1848598448143597568
score 12.976206

Publicaciones similares