Engineering Research Center of Key Technique for Biotherapy of Guangdong Province, Shantou University Medical College, Shantou 515041, China.
Engineering Research Center of Key Technique for Biotherapy of Guangdong Province, Shantou University Medical College, Shantou 515041, China; Department of Neurosurgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, China.
Ecotoxicol Environ Saf. 2024 Sep 15;283:116862. doi: 10.1016/j.ecoenv.2024.116862. Epub 2024 Aug 10.
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.
雌激素和类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引起了越来越多的关注。然而，目前，EDCs 对神经和血管发育的潜在毒性机制仍在全面研究中。在研究中，我们利用斑马鱼来评估不同雌激素对发育中神经和血管的毒性。结果表明，用不同雌激素处理的斑马鱼，特别是 E2，表现出发育畸形，包括死亡率增加、体长减少、心率降低、游泳行为异常以及发育畸形增加，包括脊柱弯曲（SC）、卵黄水肿（YE）和心包水肿（PE），呈剂量依赖性，在 72 h 处理时最为明显。进一步的形态学评估显示，E2 暴露显著诱导了斑马鱼胚胎的运动神经元异常。此外，这三种雌激素处理还损害了斑马鱼胚胎早期的血管发育。在机制上，下游因子的鉴定表明，在雌激素暴露后，几种关键的神经和血管发育相关基因，包括 syn2a、gfap、gap43、shha、kdr、flt1 和 flt4，在转录水平上被下调，表明雌激素暴露可能通过干扰与神经和血管发育相关的基因的 mRNA 水平引起神经和血管毒性。
