Assessment of developmental toxicity and the potential mode of action underlying single and binary exposure to estrogenic endocrine disrupting chemicals in zebrafish (Danio rerio)

Comp Biochem Physiol C Toxicol Pharmacol. 2023 Dec 19:109821. doi: 10.1016/j.cbpc.2023.109821. Online ahead of print.ABSTRACTThe current study investigated the effect of single and binary exposure to distinct xenoestrogens, including diethylstilbestrol (DES) and zearalenone (ZEN), on zebrafish embryos subjected to continuous exposure for 4 days starting from 4 h post fertilization. Noteworthy impact on cumulative mortality, hatchability, spinal and tail curvature, pericardial edema, and reduction in blood circulation were observed in DES-treated embryos, with lower incidence and intensity shown for ZEN at the same nominal concentration (3 μM). An interactive effect was seen for the combined exposure to DES and ZEN, in which deformities and circulatory failure mediated by DES were mitigated by co-treatment with low concentrations of ZEN. Similarly, ZEN-induced spinal and tail curvature, pericardial edema, and blood flow reduction declined dramatically following DES co-exposure at low concentrations. A significant counteracting effect has been observed against DES- and ZEN-induced developmental anomalies following co-treatment with an estrogen receptor (ER) antagonist, fulvestrant (FUL). The assessment of the aromatase gene (CYP19A1b) showed that DES strongly upregulated mRNA expression of CYP19A1b with a lower EC50 (1.1 × 10-3 nM) than a natural estrogen, 17β-estradiol (2.5 nM). Similarly, ZEN induced CYP19A1b mRNA expression with an EC50 of 57 nM. Exposure to 10 or 20 μM ...
Source: Comparative biochemistry and physiology. Toxicology and pharmacology : CBP - Category: Biochemistry Authors: Source Type: research