Paternal intergenerational thyroid disruption in zebrafish induced by environmental prednisone exposure

Environmental pollutants adversely affect both adult organisms and their offspring. Prednisone, a synthetic glucocorticoid frequently detected in surface water, harms aquatic organisms like sheepshead minnows, tadpoles, and zebrafish (Danio rerio). However, data on its effects on the thyroid endocrine system of zebrafish and its intergenerational toxicity are currently lacking. This study exposed adult male zebrafish to environmentally relevant prednisone concentrations (0-500 ng/L) for 60 days to explore potential thyroid endocrine disruption in both parents and offspring. Research findings show that compared with the control group, zebrafish in the high-dose (H) group had significantly reduced body length and weight. Their swimming speed decreased by 20.9-32.7%, the time spent stationary at the bottom of the tank decreased by 139.1-152.1%, and the frequency of this behavior dropped by 84.6-94.2%. As prednisone concentrations increased, the plasma levels of T4 in parental zebrafish decreased significantly, while the levels of T3 and TSH increased significantly. Thyroid follicular epithelial cells exhibited hyperplasia and hypertrophy along with a depletion of colloid cells. These effects were associated with abnormal transcriptional levels of genes involved in the hypothalamic-pituitary-thyroid (HPT) axis (i.e., crh, pax8, tpo, tg, ttr and dio1 and dio2). Additionally, parental exposure to prednisone impaired F1 larvae: 82.3% increased mortality, 14.3-32.2% reduced hatching rates, abnormal heart rates, 29.16-38.76% reduced swimming activity, decreased thyroid hormones, and dysregulated transcription of HPT axis-related genes. The study confirms that prednisone induces intergenerational toxicity in parents and offspring by disrupting thyroid endocrine function, enhancing understanding of the risks posed by prednisone to fish.