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Platform for Preclinical Contract Male Reproductive Toxicity Testing Using Acr-Luc Knock-In Mice

An In Vivo and In Vitro Assay for Longitudinal and Quantitative Assessment of Spermatogenic Failure and Recovery via Spermatogenic Cell-Specific Acrosin (Acr) Promoter-Driven Luciferase Expression.

Advantages

‐Enhanced Efficiency & Cost Reduction: Drastically reduces animal usage via continuous data collection (promoting 3Rs), cutting housing, management, and labor expenses.
‐Superior Penetration & Quantification: Overcomes conventional fluorescence limitations to deliver highly accurate bioluminescent quantification in deep testicular tissue.
‐Expanded Contract Screening: Enables high-throughput primary screening through an isolated primary spermatogenic cell evaluation system.

Current Stage and Key Data

Fully established in vivo and in vitro evaluation systems with validated Proof of Concept (PoC):
- Spermatogenic Cell Correlation: Strong positive correlation between primary spermatogenic cell counts and bioluminescence intensity.
- Long-Term In Vivo Stability: Stable bioluminescence maintained across aging individuals (44+ weeks) with zero background fluctuation.
- Quantification of Damage & Recovery: Clear dose-dependent signal suppression and differentiation between reversible and irreversible damage in X-ray irradiation models.
- Toxicity Assays: Successfully detected time-course spermatogenic cell reduction from anticancer agents (Trichostatin A) and endocrine disruptors (Bisphenol A).

Partnaring Model

Patent/know-how licensing for integration into contract testing services.
- Adding high value and differentiation to contract reproductive toxicity and safety testing services for pharmaceutical and chemical clients
- Expanding contract assay service portfolios covering both in vitro and in vivo platforms
- Providing next-generation testing services compliant with clients' animal welfare standards (3Rs) and ESG requirements.

Background and Technology

Traditional CRO reproductive toxicity studies rely on labor-intensive, time-consuming methods requiring large animal cohorts and euthanasia, creating significant 3Rs (Reduction) hurdles. Furthermore, conventional fluorescent models lack tissue penetration for deep-organ in vivo tracking like the testes. The Acr-Luc KI bioluminescent mouse model and primary cell assay platform overcome these limitations by offering deep-tissue penetration and precise quantification—delivering a highly efficient, sustainable, and commercially valuable solution for contract safety testing.

Principal Investigator

Hisanori Fukunaga (Graduate School of Health Science, Hokkaido University)

Patents and Publications

- Patent pending
- Information on related literature is included in the materials. Please click the “Iinterested in this technology? [Download Materials]” button below to download and view the materials.

Project No:bk-05351d