Okadaic Acid Exposure Induced Neural Tube Defects in Chicken (Gallus gallus) Embryos.
Okadaic Acid Exposure Induced Neural Tube Defects in Chicken (Gallus gallus) Embryos.
复制标题
冈田酸暴露诱发鸡胚胎神经管缺陷
DOI：
10.3390/md19060322
复制
发表时间：
2021-06-02
期刊：
影响因子：
5.4
通讯作者：
Yang W
中科院分区：
文献类型：
--
作者：
Jiao Y;Wang G;Li D;Li H;Liu J;Yang X;Yang W
冈田酸（Okadaic acid，OA）是一种重要的脂溶性贝类毒素，广泛分布于世界各地，是引起人类贝类中毒的主要原因。它具有多种毒性，包括细胞毒性、胚胎毒性、神经毒性，甚至遗传毒性。然而，没有直接证据表明其对人类后代的发育毒性。本研究以鸡胚为动物模型，探讨OA暴露对神经发生和神经管畸形发生率的影响。我们发现OA暴露可引起神经管畸形并抑制神经元分化。pHI 3和c-Caspase 3免疫荧光染色结果显示OA可促进神经管细胞增殖，抑制神经管细胞凋亡。此外，OA处理后，Nrf 2表达下调，活性氧（ROS）含量和超氧化物歧化酶（SOD）活性升高，表明OA可导致早期鸡胚氧化应激，从而增加后续NTDs的风险。骨形态发生蛋白4（BMP 4）和Sonic hedgehog（Shh）在背侧神经管中表达的抑制表明OA还可以影响背外侧铰链点的形成，这可能最终阻碍神经管的闭合。转录组和qPCR分析显示，OA诱导的NTDs与Toll样受体信号通路中的脂多糖结合蛋白（LBP）、转录因子AP-1（JUN）、原癌基因蛋白c-fos（FOS）和C-C基序趋化因子4（CCL 4）的表达显著增加，提示OA诱导的NTDs可能与Toll样受体信号通路有关。综上所述，我们的研究结果可以促进对OA对人类妊娠的胚胎-胎儿发育毒性的理解。
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.
登录
查看更多内容
影响因子：
1.2
作者：
Ertekin, T.;Bilir, A.;Albay, S.
通讯作者：
Albay, S.
DOI：
10.1002/0471140856.tx1304s14
发表时间：
2003-02-01
期刊：
Current protocols in toxicology
影响因子：
--
作者：
Henshel, Diane S;DeWitt, Jamie;Troutman, Andrea
通讯作者：
Troutman, Andrea
DOI：
10.1002/neu.480260312
发表时间：
1995-03-01
期刊：
JOURNAL OF NEUROBIOLOGY
影响因子：
--
作者：
CURRAN, T;MORGAN, JI
通讯作者：
MORGAN, JI
影响因子：
64.8
作者：
HENRIQUE, D;ADAM, J;ISHHOROWICZ, D
通讯作者：
ISHHOROWICZ, D
DOI：
10.1080/15287394.2020.1793046
发表时间：
2020-07-18
影响因子：
2.6
作者：
Figueroa, Diego;Signore, Ailen;Garcia, Carlos
通讯作者：
Garcia, Carlos