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Cited by 444

The DOI matches its Crossref record; 94 of the 94 references it cites were found in a registry or an index.

Glyphosate-Based Herbicides Produce Teratogenic Effects on Vertebrates by Impairing Retinoic Acid Signaling

Open access
Paganelli, Alejandra, Gnazzo, Victoria, Acosta, Helena, López, Silvia L., Carrasco, Andrés E.·2010·Chemical Research in Toxicology
DOI 10.1021/tx1001749
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Abstract

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.

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Metadata

Authors
Paganelli, A., Gnazzo, V., Acosta, H., López, S. L., & Carrasco, A. E.
Venue
Chemical Research in Toxicology
Publisher
American Chemical Society (ACS)
Published
2010-08-09
Volume
23
Issue
10
Pages
1586-1595
ISSN
  • 0893-228X (ISSN-L)
  • 1520-5010
DOI
10.1021/tx1001749
OpenAlex
W2111629741
Cited by
444
References
94
FWCI
25.47
Type
journal article
Language
en
Open access
green

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