Significance: Why some animals, but not others, respond to injury with extensive regeneration is an outstanding question and attracts considerable research interest. Planarian flatworms possess a polarity system throughout their anteroposterior axis that specifies the identity of missing tissues at wound sites. The regeneration of vertebrate appendages involves distal growth. However, whether vertebrate appendages can undergo bidirectional regeneration along the proximodistal axis remains unclear. Our study demonstrates that unidirectional blastema regeneration polarity occurs in zebrafish fins along the proximodistal axis. We identified calcineurin as a molecular switch that specifies the blastema of the PCE and controls regeneration polarity in zebrafish fins. Our results are of great importance for future regeneration polarity studies on vertebrates.

Due to the widely application of Cyclosporine A (CsA) as an immunosuppressant in clinic, it is necessary to study its potential toxicity. Therefore, we used zebrafish as a model animal to evaluate the toxicity of CsA on embryonic development. Exposure of zebrafish embryos to CsA at concentrations of 5 mg/L, 10 mg/L, and 15 mg/L from 12 hpf to 72 hpf resulted in abnormal embryonic development, including cardiac malformation, pericardial edema, decreased heart rate, decreased blood flow velocity, deposition at yolk sac, shortened body length, and increased distance between venous sinus and arterial bulb (SV-BA). The expression of genes related to cardiac development was disordered, and the apoptotic genes were up-regulated. Oxidative stress level was up-regulated and accumulated in pericardium in a dose-dependent manner. Astaxanthin (ATX) treatment could significantly alleviate zebrafish heart defects. CsA induced up-regulation of Wnt signaling in zebrafish, and IWR-1, an inhibitor of Wnt signaling pathway, could effectively rescue the heart defects induced by CsA. Together, our study indicated that CsA induced cardiac developmental toxicity in zebrafish larvae through up-regulating oxidative stress and Wnt signaling, contributing to a more comprehensive evaluation of the safety of the drug.

Iprodione is an effective and broad-spectrum fungicide commonly used for early disease control in fruit trees and vegetables. Due to rainfall, iprodione often finds its way into water bodies, posing toxicity risks to non-target organisms and potentially entering the human food chain. However, there is limited information available regarding the developmental toxicity of iprodione specifically on the liver in existing literature. In this study, we employed larval and adult zebrafish as models to investigate the toxicity of iprodione. Our findings revealed that iprodione exposure led to yolk sac edema and increased mortality in zebrafish. Notably, iprodione exhibited specific effects on zebrafish liver development. Additionally, zebrafish exposed to iprodione experienced an overload of reactive oxygen species, resulting in the upregulation of p53 gene expression. This, in turn, triggered hepatocyte apoptosis and disrupted carbohydrate/lipid metabolism as well as energy demand systems. These results demonstrated the substantial impact of iprodione on zebrafish liver development and function. Furthermore, the application of astaxanthin (an antioxidant) and p53 morpholino partially mitigated the liver toxicity caused by iprodione. To summarize, iprodione induces apoptosis through the upregulation of p53 mediated by oxidative stress signals, leading to liver toxicity in zebrafish. Our study highlights that exposure to iprodione can result in hepatotoxicity in zebrafish, and it may potentially pose toxicity risks to other aquatic organisms and even humans.

Reproductive system diseases have become a major health challenge facing humans, so extensive investigations are needed to understand their complex pathogenesis and summarize effective treatments. In the study of reproductive diseases, mice are the most commonly used animal model. However, the cost and time required to establish mouse animal models are high. The existing zebrafish model can solve this problem well. Zebrafish is an animal model with great application prospects and has lots of advantages, including high degree of genetic conservation with humans, short reproductive cycle, transparent embryos, and rapid growth, providing unique opportunities for high-throughput drug screening and identification of potential treatments. Researchers have successfully used chemical induction, physical damage, gene editing technology, etc., to induce reproductive system damage in zebrafish to study the biological processes related to its reproductive diseases. Therefore, in this review, the main models and related advantages of zebrafish in reproductive diseases are summarized, the pathological mechanisms of zebrafish as a reproductive disease model are clarified, and new perspectives and valuable insights are provided for the treatment of human reproductive diseases. The literature and data cited in the review are all from PubMed, covering important research results on zebrafish reproductive diseases in the past 10 years.