Spirhanzlova Petra, Couderq Stephan, Le Mével Sébastian, Leemans Michelle, Krief Sabrina, Mughal Bilal B, Demeneix Barbara A, Fini Jean-Baptiste
Unité PhyMA Laboratory, Adaptation du Vivant, Muséum National d'Histoire Naturelle, Paris, France.
Unité Eco-Anthropologie, Hommes et Environnements, Muséum National d'Histoire Naturelle, Musée de l'Homme, Paris, France.
Neuroendocrinology. 2023;113(12):1298-1311. doi: 10.1159/000525719. Epub 2022 Jun 24.
The extensive use of the insecticide chlorpyrifos (CPF) throughout the world has brought increased scrutiny on its environmental and health impact. CPF is a cholinergic neurotoxicant; however, exposure to low noncholinergic doses is associated with numerous neurodevelopmental effects in animal models. In this study, we aimed to assess CPF for its potential to disrupt thyroid hormone signalling and investigate the short- and long-term effects on neurodevelopment by using Xenopus laevis.
The thyroid hormone (TH) disrupting potential of CPF was assessed using TH-sensitive transgenic Tg(thibz:eGFP) tadpoles. The consequences of early embryonic exposure were examined by exposing fertilized eggs for 72 h to environmentally relevant CPF concentrations (10-10 M and 10-8 M). Three endpoints were evaluated: (1) gene expression in whole embryonic brains immediately after exposure, (2) mobility and brain morphology 1 week after exposure, and (3) brain morphology and axon diameters at the end of metamorphosis (2 months after the exposure).
CPF disrupted TH signalling in Tg(thibz:eGFP) tadpoles. The expression of genes klf9, cntn4, oatp1c1, and tubb2b was downregulated in response to CPF. Tadpoles exposed to CPF exhibited increased mobility and altered brain morphology compared to control tadpoles. Early embryonic exposure of CPF affected myelinated axon diameter, with exposed animals exhibiting shifted frequency distributions of myelinated axons diameters towards smaller diameters in the hindbrain of froglets.
DISCUSSION/CONCLUSION: This study provides more evidence of the endocrine and neurodevelopment disrupting activity of CPF. Further experimental and epidemiological studies are warranted to determine the long-term consequences of early CPF exposure on brain development.
杀虫剂毒死蜱（CPF）在全球的广泛使用使其对环境和健康的影响受到了更多审视。CPF是一种胆碱能神经毒剂；然而，在动物模型中，低剂量非胆碱能暴露与众多神经发育效应相关。在本研究中，我们旨在评估CPF干扰甲状腺激素信号传导的潜力，并利用非洲爪蟾研究其对神经发育的短期和长期影响。
使用对甲状腺激素（TH）敏感的转基因Tg(thibz:eGFP)蝌蚪评估CPF干扰TH的潜力。通过将受精卵暴露于环境相关浓度的CPF（10-10 M和10-8 M）72小时，研究早期胚胎暴露的后果。评估了三个终点：（1）暴露后立即在整个胚胎脑中的基因表达，（2）暴露1周后的运动能力和脑形态，以及（3）变态结束时（暴露后2个月）的脑形态和轴突直径。
CPF干扰了Tg(thibz:eGFP)蝌蚪中的TH信号传导。klf9、cntn4、oatp1c1和tubb2b基因的表达因CPF而下调。与对照蝌蚪相比，暴露于CPF的蝌蚪运动能力增强且脑形态改变。CPF的早期胚胎暴露影响了有髓轴突直径，暴露动物的有髓轴突直径频率分布在后脑向较小直径偏移。
讨论/结论：本研究提供了更多关于CPF内分泌和神经发育干扰活性的证据。有必要进行进一步的实验和流行病学研究，以确定早期CPF暴露对脑发育的长期后果。
