Cargando…
Okadaic Acid Exposure Induced Neural Tube Defects in Chicken (Gallus gallus) Embryos
Okadaic acid (OA) is an important liposoluble shellfish toxin distributed worldwide, and is mainly responsible for diarrheic shellfish poisoning in human beings. It has a variety of toxicities, including cytotoxicity, embryonic toxicity, neurotoxicity, and even genotoxicity. However, there is no dir...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227060/ https://www.ncbi.nlm.nih.gov/pubmed/34199615 http://dx.doi.org/10.3390/md19060322 |
_version_ | 1783712435492880384 |
---|---|
author | Jiao, Yuhu Wang, Guang Li, Dawei Li, Hongye Liu, Jiesheng Yang, Xuesong Yang, Weidong |
author_facet | Jiao, Yuhu Wang, Guang Li, Dawei Li, Hongye Liu, Jiesheng Yang, Xuesong Yang, Weidong |
author_sort | Jiao, Yuhu |
collection | PubMed |
description | Okadaic acid (OA) is an important liposoluble shellfish toxin distributed worldwide, and is mainly responsible for diarrheic shellfish poisoning in human beings. It has a variety of toxicities, including cytotoxicity, embryonic toxicity, neurotoxicity, and even genotoxicity. However, there is no direct evidence of its developmental toxicity in human offspring. In this study, using the chicken (Gallus gallus) embryo as the animal model, we investigated the effects of OA exposure on neurogenesis and the incidence of neural tube defects (NTDs). We found that OA exposure could cause NTDs and inhibit the neuronal differentiation. Immunofluorescent staining of pHI3 and c-Caspase3 demonstrated that OA exposure could promote cell proliferation and inhibit cell apoptosis on the developing neural tube. Besides, the down-regulation of Nrf2 and increase in reactive oxygen species (ROS) content and superoxide dismutase (SOD) activity in the OA-exposed chicken embryos indicated that OA could result in oxidative stress in early chick embryos, which might enhance the risk of the subsequent NTDs. The inhibition of bone morphogenetic protein 4 (BMP4) and Sonic hedgehog (Shh) expression in the dorsal neural tube suggested that OA could also affect the formation of dorsolateral hinge points, which might ultimately hinder the closure of the neural tube. Transcriptome and qPCR analysis showed the expression of lipopolysaccharide-binding protein (LBP), transcription factor AP-1 (JUN), proto-oncogene protein c-fos (FOS), and C-C motif chemokine 4 (CCL4) in the Toll-like receptor signaling pathway was significantly increased in the OA-exposed embryos, suggesting that the NTDs induced by OA might be associated with the Toll-like receptor signaling pathway. Taken together, our findings could advance the understanding of the embryo–fetal developmental toxicity of OA on human gestation. |
format | Online Article Text |
id | pubmed-8227060 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-82270602021-06-26 Okadaic Acid Exposure Induced Neural Tube Defects in Chicken (Gallus gallus) Embryos Jiao, Yuhu Wang, Guang Li, Dawei Li, Hongye Liu, Jiesheng Yang, Xuesong Yang, Weidong Mar Drugs Article Okadaic acid (OA) is an important liposoluble shellfish toxin distributed worldwide, and is mainly responsible for diarrheic shellfish poisoning in human beings. It has a variety of toxicities, including cytotoxicity, embryonic toxicity, neurotoxicity, and even genotoxicity. However, there is no direct evidence of its developmental toxicity in human offspring. In this study, using the chicken (Gallus gallus) embryo as the animal model, we investigated the effects of OA exposure on neurogenesis and the incidence of neural tube defects (NTDs). We found that OA exposure could cause NTDs and inhibit the neuronal differentiation. Immunofluorescent staining of pHI3 and c-Caspase3 demonstrated that OA exposure could promote cell proliferation and inhibit cell apoptosis on the developing neural tube. Besides, the down-regulation of Nrf2 and increase in reactive oxygen species (ROS) content and superoxide dismutase (SOD) activity in the OA-exposed chicken embryos indicated that OA could result in oxidative stress in early chick embryos, which might enhance the risk of the subsequent NTDs. The inhibition of bone morphogenetic protein 4 (BMP4) and Sonic hedgehog (Shh) expression in the dorsal neural tube suggested that OA could also affect the formation of dorsolateral hinge points, which might ultimately hinder the closure of the neural tube. Transcriptome and qPCR analysis showed the expression of lipopolysaccharide-binding protein (LBP), transcription factor AP-1 (JUN), proto-oncogene protein c-fos (FOS), and C-C motif chemokine 4 (CCL4) in the Toll-like receptor signaling pathway was significantly increased in the OA-exposed embryos, suggesting that the NTDs induced by OA might be associated with the Toll-like receptor signaling pathway. Taken together, our findings could advance the understanding of the embryo–fetal developmental toxicity of OA on human gestation. MDPI 2021-06-02 /pmc/articles/PMC8227060/ /pubmed/34199615 http://dx.doi.org/10.3390/md19060322 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Jiao, Yuhu Wang, Guang Li, Dawei Li, Hongye Liu, Jiesheng Yang, Xuesong Yang, Weidong Okadaic Acid Exposure Induced Neural Tube Defects in Chicken (Gallus gallus) Embryos |
title | Okadaic Acid Exposure Induced Neural Tube Defects in Chicken (Gallus gallus) Embryos |
title_full | Okadaic Acid Exposure Induced Neural Tube Defects in Chicken (Gallus gallus) Embryos |
title_fullStr | Okadaic Acid Exposure Induced Neural Tube Defects in Chicken (Gallus gallus) Embryos |
title_full_unstemmed | Okadaic Acid Exposure Induced Neural Tube Defects in Chicken (Gallus gallus) Embryos |
title_short | Okadaic Acid Exposure Induced Neural Tube Defects in Chicken (Gallus gallus) Embryos |
title_sort | okadaic acid exposure induced neural tube defects in chicken (gallus gallus) embryos |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227060/ https://www.ncbi.nlm.nih.gov/pubmed/34199615 http://dx.doi.org/10.3390/md19060322 |
work_keys_str_mv | AT jiaoyuhu okadaicacidexposureinducedneuraltubedefectsinchickengallusgallusembryos AT wangguang okadaicacidexposureinducedneuraltubedefectsinchickengallusgallusembryos AT lidawei okadaicacidexposureinducedneuraltubedefectsinchickengallusgallusembryos AT lihongye okadaicacidexposureinducedneuraltubedefectsinchickengallusgallusembryos AT liujiesheng okadaicacidexposureinducedneuraltubedefectsinchickengallusgallusembryos AT yangxuesong okadaicacidexposureinducedneuraltubedefectsinchickengallusgallusembryos AT yangweidong okadaicacidexposureinducedneuraltubedefectsinchickengallusgallusembryos |