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Immunostaining of Dissected Zebrafish Embryonic Heart
Published on: January 10, 2012
Early statin exposure influences cardiac and skeletal development with implications for ion channel transcriptomes in
Ying Zhao1, Hou-Zhi Yang2, Huinan Li3
1School of Medicine, Nankai University, Tianjin, China.
Abstract:
Statins, widely prescribed for cholesterol management by inhibiting HMG-CoA reductase in the cholesterol biosynthesis pathway, may also influence vertebrate development. In this study, we investigated the developmental effects of two widely used statins, atorvastatin (ATO) and pravastatin (PRA), on zebrafish offspring. For ATO, we administered doses classified as low (1 μM), medium (5 μM), and high (10 μM), while for PRA, the corresponding concentrations were set at low (18 μM), medium (180 μM), and high (270 μM). Our results showed significant reductions in birth and hatching rates, along with decreased body length in offspring at all ATO concentrations and medium to high PRA concentrations. A notable increase in malformation rates, especially in the spine and heart, was observed across all ATO treatments and in medium and high PRA groups. Additionally, we observed reduced heart contraction rates, decreased heart size, lower bone volumes, and diminished expression of mRNA osteogenic markers. Elevated venous sinus-artery bulb (SV-BA) ratios, increased thoracic area, and abnormal cartilage development were also prominent in all ATO-treated groups. Transcriptome analysis revealed alterations in genes predominantly associated with ion channels. These findings provide insights into the potential impacts of specific concentrations of statins on offspring development and highlight potential gene interactions with statins.
Insights
Statins like atorvastatin and pravastatin negatively impacted zebrafish development, reducing birth rates and causing malformations. These findings highlight potential risks of statin exposure during vertebrate development.
Area of Science:
- Developmental Biology
- Pharmacology
- Genetics
Background:
- Statins are cholesterol-lowering drugs that inhibit HMG-CoA reductase.
- Potential impacts of statins on vertebrate development are not fully understood.
Purpose of the Study:
- To investigate the developmental effects of atorvastatin (ATO) and pravastatin (PRA) on zebrafish offspring.
- To identify specific developmental parameters affected by varying statin concentrations.
Main Methods:
- Zebrafish embryos were exposed to different concentrations of ATO (1-10 μM) and PRA (18-270 μM).
- Evaluated outcomes included birth/hatching rates, body length, malformations, cardiac function, bone development, and gene expression.
- Transcriptome analysis was performed to identify affected pathways.
Main Results:
- Reduced birth/hatching rates and body length observed with ATO and higher PRA doses.
- Increased spinal and cardiac malformations noted across most statin treatments.
- Decreased heart contraction, smaller heart size, reduced bone volume, and altered osteogenic marker expression were evident.
- Elevated SV-BA ratios, increased thoracic area, abnormal cartilage, and ion channel gene alterations were found.
Conclusions:
- Specific concentrations of ATO and PRA adversely affect zebrafish development.
- Statins can induce malformations and impact cardiovascular and skeletal development.
- Ion channel gene expression is a potential target of statin-induced developmental toxicity.
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