Longitudinal Analysis of Male Fertility Using an Acr-Luc Knock-In Mouse Model: A Preclinical Platform for...

Area of Science:

• Reproductive toxicology
• Biomedical engineering
• Genetically engineered models

Background:

• Reproductive toxicity testing is crucial for assessing xenobiotics but current methods are labor-intensive and require many animals.
• Acrosin, vital for sperm function, is expressed specifically in germ cells.

Purpose of the Study:

• To develop a novel, non-invasive imaging platform for reproductive toxicity assessment.
• To create a genetically engineered mouse model for real-time monitoring of spermatogenesis.

Main Methods:

• Generated an Acrosin-Luciferase (Acr-Luc) knock-in mouse model using the Acrosin promoter to drive Luciferase expression.
• Utilized bioluminescence imaging for longitudinal and quantitative assessment of spermatogenesis.
• Evaluated the model's efficacy in detecting radiation-induced male fertility impairments.

Main Results:

• The Acr-Luc KI model enables real-time, longitudinal imaging of spermatogenesis via bioluminescence.
• The platform accurately captures radiation-induced male fertility disruptions without terminal analysis.
• This approach reduces animal use and interindividual variability, offering high temporal resolution for onset and recovery phases.

Conclusions:

• The Acr-Luc KI mouse model provides a reliable, non-invasive preclinical platform for reproductive toxicity testing.
• This model significantly advances studies in reproductive biology, toxicology, and oncofertility research.
• It aligns with the 3Rs principles by reducing animal use and improving data reliability.