药物和其他化学物质会影响器官发生,在怀孕期间或出生后暴露于早产儿。向有早产风险的孕妇施用皮质类固醇以降低新生儿发病率和死亡率。此外,大剂量皮质类固醇经常暴露于早产儿,以维持血压和预防和治疗支气管肺发育不良,早产婴儿的一种慢性肺病。尽管有临床益处,有越来越多的证据表明皮质类固醇介导的短期和长期有害的发育效应,尤其是肾脏.这里,我们对皮质类固醇介导的幼体斑马鱼pronephros发育影响进行了详细的形态学和功能分析。受精后24小时(hpf)转基因Tg(wt1b:EGFP)斑马鱼幼虫暴露于一组天然和合成的皮质类固醇(氢化可的松,地塞米松,6α-甲基强的松龙,倍他米松,泼尼松龙,氟氢可的松,11-脱氧皮质酮)在不同浓度下具有不同的糖皮质激素和盐皮质激素效力24小时。一个半自动化的,多参数体内工作流程可同时评估肾脏形态,肾FITC-菊粉清除率,和同一幼虫内的心率。所有皮质类固醇对pronephros发育均具有显著的形态和功能作用,包括前肾小球的显着肥大以及FITC-菊粉清除率的剂量依赖性增加,作为肾小球滤过率的标志。总之,本研究表明,皮质类固醇暴露对幼体斑马鱼的肾脏发育和功能有显著影响。因此,这些研究强调,由于可能对肾脏造成短期和长期伤害,因此应仔细考虑胎儿和早产新生儿的糖皮质激素暴露.
Pharmaceutical drugs and other chemicals can impact organogenesis, either during pregnancy or by postnatal exposure of very preterm infants. Corticosteroids are administered to pregnant women at risk of preterm delivery in order to reduce neonatal morbidity and mortality. In addition, high-dose corticosteroid exposure of very preterm infants regularly serves to maintain blood pressure and to prevent and treat bronchopulmonary dysplasia, a form of chronic lung disease in prematurely born infants. Despite clinical benefits, there is increasing evidence of corticosteroid-mediated short- and long-term detrimental developmental effects, especially in the kidney. Here, we performed a detailed morphological and functional analysis of corticosteroid-mediated effects on pronephros development in larval zebrafish. 24 hours post fertilization (hpf) transgenic Tg(wt1b: EGFP) zebrafish larvae were exposed to a set of natural and synthetic corticosteroids (hydrocortisone, dexamethasone, 6α-methylprednisolone, betamethasone, prednisolone, fludrocortisone, 11-deoxycorticosterone) with varying glucocorticoid and mineralocorticoid potency for 24 hours at different concentrations. A semi-automated, multiparametric in vivo workflow enabled simultaneous assessment of kidney morphology, renal FITC-inulin clearance, and heart rate within the same larva. All corticosteroids exerted significant morphological and functional effects on pronephros development, including a significant hypertrophy of the pronephric glomeruli as well as dose-dependent increases in FITC-inulin clearance as a marker of glomerular filtration rate. In conclusion, the present study demonstrates a significant impact of corticosteroid exposure on kidney development and function in larval zebrafish. Hence, these studies underline that corticosteroid exposure of the fetus and the preterm neonate should be carefully considered due to potential short- and long-term harm to the kidney.