17β-Trenbolone exposure programs metabolic dysfunction in larval medaka.

Area of Science:

• Environmental Toxicology
• Endocrinology
• Fish Biology

Background:

• 17β-trenbolone (TB) is an anabolic steroid with potential environmental impacts.
• Early life stages of aquatic organisms are particularly vulnerable to endocrine disruptors.

Purpose of the Study:

• To investigate the physiological and transcriptomic effects of TB exposure on early-stage medaka (Oryzias latipes).
• To assess TB's impact on sex determination, metabolism, and gene expression related to metabolic pathways.

Main Methods:

• Medaka larvae were exposed to various TB concentrations.
• Physiological assessments included sex reversal rates, gonadosomatic index, and body mass index.
• Transcriptomic analysis (microarray) identified differentially expressed genes and affected metabolic pathways using KEGG Orthology Database.

Main Results:

• TB exposure caused dose-dependent sex reversal, reaching 100% males at 200 ng/L.
• Female medaka exhibited increased gonadosomatic index, obesity, and reduced fertility.
• Upregulated genes were associated with lipid metabolism and cholesterol biosynthesis (mevalonate pathway).
• Downregulated genes included angiopoietin-like 4 and mitochondrial uncoupling protein 1, linked to obesity regulation.

Conclusions:

• Early-life exposure to TB can induce significant metabolic dysfunctions in female medaka, including obesity and disrupted cholesterol synthesis.
• TB acts as an endocrine disruptor, affecting sexual development and metabolic homeostasis in fish.