Metabolomics-based pathway changes in testis fragments treated with ethinylestradiol in vitro

Area of Science:

• Reproductive Toxicology
• In Vitro Models
• Metabolomics

Background:

• Need for in vitro models to assess male reproductive toxicity.
• Evaluation of a mouse testis organ culture system.
• Limited differentiation but suitable for histopathology and metabolomics.

Purpose of the Study:

• Assess the utility of an in vitro mouse testis organ culture model for toxicity testing.
• Investigate the effects of ethinylestradiol (EE) on testicular metabolism.
• Identify potential biomarkers of male reproductive toxicity.

Main Methods:

• Postnatal Day 5 mouse testes cultured in vitro.
• Treatment with varying concentrations of ethinylestradiol (EE).
• Analysis of metabolome changes using liquid chromatography/mass spectrometry (LC/MS) and histology.

Main Results:

• Significant alterations in metabolites related to glycogen metabolism, glycolysis, and the TCA cycle observed with EE treatment.
• Metabolite changes correlated with increased seminiferous tubules containing round spermatids.
• Dose-dependent increase in cell death was noted.

Conclusions:

• Ethinylestradiol (EE) may induce testicular toxicity by disrupting energy metabolism pathways.
• The in vitro testis model shows promise for identifying chemicals affecting male reproductive health.
• Further studies with other toxicants are warranted to validate the model.