雌激素和雌激素化学物质是内分泌干扰化学物质(EDCs)。EDCs对人类和水生生物的潜在毒性已日益引起人们的关注。然而,目前,EDC对神经和血管发育的潜在毒性机制仍在充分研究中。在研究期间,我们利用斑马鱼评估不同雌激素的发育神经和血管毒性。结果表明,不同雌激素处理的斑马鱼,尤其是E2,表现出发育畸形,包括死亡率上升,身体长度减少,心率下降,游泳行为异常,发育畸形增加,包括脊柱弯曲(SC),蛋黄水肿(YE)和周围水肿(PE),以剂量依赖性方式治疗72小时。进一步的形态学评估显示,E2暴露显着诱导斑马鱼胚胎的运动神经异常。此外,用这三种雌激素治疗也会损害斑马鱼胚胎早期的血管发育。机械上,下游因子的鉴定揭示了几个关键的神经和血管发育相关基因,包括syn2a,gfap,gap43,shha,kdr,flt1和flt4在斑马鱼雌激素暴露后转录下调,提示雌激素暴露可能通过干扰神经和血管发育相关基因的mRNA水平而引起神经和血管毒性。
Estrogens and estrogenic chemicals are endocrine-disrupting chemicals (EDCs). The potential toxicity of EDCs to humans and aquatic organisms has become increasingly concerning. However, at present, the potential toxic mechanisms of EDCs on neural and vascular development are still being fully investigated. During the study, we utilized zebrafish to assess the developmental neural and vascular toxicity of different estrogens. The results indicated that zebrafish treated with different estrogens, especially E2, exhibit developmental malformations, including increased mortality, decreased body length, decreased heart rate, aberrant swimming behavior, and increased developmental malformations, including spinal curvature (SC), yolk edema (YE) and pericaidial edema (PE), in a dose-dependent manner with 72 h-treated. Further morphological evaluation revealed that E2 exposure significantly induced motor neural abnormalities in zebrafish embryos. In addition, treated with these three estrogens also impaired the vascular development in the early stage of zebrafish embryos. Mechanistically, the identification of downstream factors revealed that several key neural and vascular development-related genes, including syn2a, gfap, gap43, shha, kdr, flt1 and flt4, were transcriptionally downregulated after estrogen exposure in zebrafish, suggesting that estrogen exposure might cause neural and vascular toxicity by interfering the mRNA levels of genes relevant to neural and vascular development.