Longitudinal analysis of male fertility using an Acr-Luc knock-in mouse model; A Preclinical platform for reproductive toxicity testing

Fukunaga, Hisanori*; Seino, Ryosuke*; Matsuya, Yusuke  ; Takashima, Hiroyuki*; Ishikawa, Masayori*; Onodera, Yasuhito*; Shirato, Hiroki*; Miyata, Haruhiko*; Prise, K. M.*

The main purpose of reproductive toxicity testing is to evaluate whether the administration of xenobiotics, such as pharmaceuticals, food additives, and environmental chemicals, exerts adverse effects on reproductive function in living organisms. The outcomes can be applied as a scientific basis to evaluate potential risks to human reproductive health. In this study, we developed a novel luciferase reporter mouse model for assessing reproductive toxicity, enabling longitudinal and quantitative evaluations of male fertility through in vivo imaging of acrosin without the need for euthanasia. This approach promises to advance our understanding of the mechanisms underlying the onset and recovery of reproductive toxicity. Additionally, reducing the number of animals needed for evaluation aligns with the principle of Reduction, which is one of the core components of the 3Rs in animal studies.