Lead acetate induces cartilage defects and bone loss in zebrafish embryos by disrupting the GH/IGF-1 axis

斑马鱼 软骨细胞 内分泌学 软骨 内科学 成骨细胞 运行x2 生物 发育毒性 毒性 男科 解剖 医学 胎儿 生物化学 基因 遗传学 怀孕 体外
作者
Rui Yan,Jie Ding,Qianlei Yang,Xiaoyun Zhang,Junyu Han,Tingxu Jin,Shudi Shi,Xirui Wang,Yu Zheng,Heran Li,Hengdong Zhang,Yan An
出处
期刊:Ecotoxicology and Environmental Safety [Elsevier]
卷期号:253: 114666-114666 被引量:7
标识
DOI:10.1016/j.ecoenv.2023.114666
摘要

Skeletal system toxicity due to lead exposure has attracted extensive attention in recent years, but few studies focus on the skeletal toxicity of lead in the early life stages of zebrafish. The endocrine system, especially the GH/IGF-1 axis, plays an important role in bone development and bone health of zebrafish in the early life. In the present study, we investigated whether lead acetate (PbAc) affected the GH/IGF-1 axis, thereby causing skeletal toxicity in zebrafish embryos. Zebrafish embryos were exposed to lead PbAc between 2 and 120 h post fertilization (hpf). At 120 hpf, we measured developmental indices, such as survival, deformity, heart rate, and body length, and assessed skeletal development by Alcian Blue and Alizarin Red staining and the expression levels of bone-related genes. The levels of GH and IGF-1 and the expression levels of GH/IGF-1 axis-related genes were also detected. Our data showed that the LC50 of PbAc for 120 h was 41 mg/L. Compared with the control group (0 mg/L PbAc), after PbAc exposure, the deformity rate increased, the heart rate decreased, and the body length was shortened at various time periods, in the 20-mg/L group at 120 hpf, the deformity rate increased by 50 fold, the heart rate decreased by 34%, and the body length shortened by 17%. PbAc altered cartilage structures and exacerbated bone loss in zebrafish embryos; in addition, PbAc exposure down-regulated the expression of chondrocyte (sox9a, sox9b), osteoblast (bmp2, runx2) and bone mineralization-related genes (sparc, bglap), and up-regulated the expression of osteoclast marker genes (rankl, mcsf). The GH level increased and the IGF-1 level declined significantly. The GH/IGF-1 axis related genes (ghra, ghrb, igf1ra, igf1rb, igf2r, igfbp2a, igfbp3, igfbp5b) were all decreased. These results suggested that PbAc inhibited the differentiation and maturation of osteoblasts and cartilage matrix, promoted the formation of osteoclasts, and ultimately induced cartilage defects and bone loss by disrupting the GH/IGF-1 axis.
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