Associate Professor Takuro Horii and Professor Izuho Hatada of the Laboratory of Genome Science, together with collaborators from Kumamoto University, RIKEN, and Yamaguchi University, have for the first time in the world demonstrated that “changes other than DNA sequence” occurring in paternal sperm can be inherited by offspring and influence their constitution and susceptibility to disease.

Traditionally, it was believed that a child’s characteristics were determined solely by the DNA sequence inherited from the parents. However, in recent years, it has been suggested that when parents are exposed to environmental factors such as stress, disease, or aging, changes occur in the information regulating gene function in sperm or eggs, and these changes may affect subsequent generations. Despite these indications, there had been no direct evidence until now.

In this study, the research team developed a novel technology that modulates the functional state of specific gene regions in sperm without altering the DNA sequence. Using this technology, they reproduced in mouse sperm a gene regulatory state similar to that associated with Silver-Russell syndrome, a condition whose mechanism of onset has not been fully understood. As a result, they confirmed that these changes were inherited by the offspring after fertilization, leading to abnormalities in growth and physical characteristics.

This groundbreaking achievement not only advances our understanding of how disease-related changes in sperm can be transmitted to the next generation but also opens the door to future development of therapies aimed at restoring abnormal sperm states to normal.

・Nature Communications
・2025/12/25
・Germline epigenome editing identifies H3K9me3 as a mediator of intergenerational DNA methylation recovery in mice

For details of the research, please click here.