A smarter approach to testing reproductive safety

Reproductive toxicity testing is part of the standard protocol for evaluating new pharmaceuticals, industrial chemicals, environmental contaminants, and radiation exposure. However, current methods require large numbers of animals and do not provide continuous or long-term data from the same individuals. A new platform could improve reproductive toxicity testing by enhancing both efficiency and ethical standards.

"Although the idea of 'glowing sperm' may sound unusual, the underlying objective is highly practical," says Dr. Hisanori Fukunaga of Hokkaido University. He is referring to the new model his team has developed to efficiently and quantitatively evaluate how pharmaceuticals, environmental chemicals, and radiation exposure could affect male reproductive function, while at the same time substantially reduce the use of animals and the associated costs.

Researchers from the Faculty of Health Sciences at Hokkaido University, along with national and international collaborators, have developed the first platform of its kind that allows dynamic visualization of male reproductive function in living mice. In findings published in Animal Welfare in January 2026, they describe an approach that enables noninvasive, real-time monitoring of male fertility over time.

They achieved this by genetically engineering mice whose sperm cells emit light. They introduced genetic material that combined a light-emitting gene with a testis-specific gene known as Acr. "By placing the luciferase reporter gene under the control of the testis-specific ACR promoter, we established a system that enables longitudinal and quantitative imaging of spermatogenesis using bioluminescence," explains Fukunaga.

The researchers then tested the new system by inducing testicular injury using X-rays. They were able to track the effects in real time, observing both the initial damage and the subsequent recovery of sperm production in the same animals.

"We were surprised by the stability and reproducibility of the luminescent signal over time," says Fukunaga. "The signals closely correlated with germ cell numbers and showed minimal variation within individuals."

The new model offers several advantages as a preclinical testing platform. Traditional reproductive toxicity studies rely on resource-intensive mating experiments. In contrast, this system allows repeated measurements in the same individuals, reducing variability and significantly lowering the number of animals required.

Beyond this, the model could also support oncofertility research, where monitoring fertility recovery after cancer treatment remains a major clinical challenge.

"At first glance, a mouse whose sperm cells emit light may seem unconventional," Fukunaga concludes. "But scientific progress often comes from turning unexpected visual phenomena into quantitative tools. Our goal was not just to create a visually striking model, but to establish a rigorous, ethical, and reproducible framework for evaluating male reproductive safety."

More information:
Yuki Otani et al, Cross-cultural variation in understanding of animal welfare principles and animal management practices among veterinary and animal welfare professionals in the UK and Japan, Animal Welfare (2025). DOI: 10.1017/awf.2025.10026

Provided by Hokkaido University