2026-02-20 ワシントン州立大学(WSU)
<関連情報>
- https://news.wsu.edu/press-release/2026/02/20/toxic-exposure-creates-disease-risk-over-20-generations/
- https://www.pnas.org/doi/10.1073/pnas.2523071123
成人発症疾患および分娩異常におけるエピジェネティックな世代間遺伝の安定性 Stability of epigenetic transgenerational inheritance of adult-onset disease and parturition abnormalities
Alexandra A. Korolenko, Eric E. Nilsson, Sarah De Santos, and Michael K. Skinner
Proceedings of the National Academy of Sciences Published:February 17, 2026
Significance
The generational stability and transmission of epigenetic alterations across twenty multiple generations in mammals was investigated. The data suggest the maternal and paternal lineages can both induce and inherit epigenetic alterations that influence disease (e.g., kidney, testis, ovary, prostate) incidence, reproductive health (e.g., parturition, infertility), and overall fitness generationally. These results provide a better understanding of the impact of environmental exposures on health outcomes generationally and impacts on evolutionary biology. The generational stability for environmental exposures to have long-term impacts on any organism’s population needs consideration. This study contributes to a growing body of evidence supporting the need for further investigation into the role of epigenetics in shaping health outcomes across generations, as well as ethical considerations surrounding environmental exposures.
Abstract
Previous research on the generational stability of epigenetic transgenerational inheritance was conducted through a ten-generation study of all transgenerational generations in mammals. This study demonstrated both the stability of epigenetic inheritance across generations and demonstrated a generational increase incidence of disease pathology. Building on this research, the present study follows the same lineage of rats with ancestral vinclozolin exposure through twenty generations. The findings offer important insights into long-term mammalian models of epigenetic transgenerational inheritance. Observations demonstrate an increase in differential DNA methylated regions across multiple generations. This indicates a persistent and stable transmission of epigenetic alterations. Additionally, deoxyuridine triphosphate (dUTP) transferase-mediated nick end labeling apoptosis assays revealed elevated levels of germline apoptosis in the male rats of the maternal and paternal lineages. This suggests a potential consequence of epigenetic dysregulation in spermatogenesis. Ancestrally exposed rats to vinclozolin showed significant parturition abnormalities in both the maternal and paternal lineages after 16 generations. This included maternal deaths during labor and stillbirths. Pathological assessments revealed abnormalities across multiple tissue types and an increased incidence of disease. This suggests the physiological consequences of the generational stability of epigenetic inheritance. Observations establish the generational stability of epigenetic inheritance over twenty generations in a mammalian model system; however, new pathology in later generations involving parturition abnormalities was also observed. The generational stability of transgenerational effects observed in this study has implications for human health, particularly regarding environmental toxicant exposures, reproductive health disorders, and disease susceptibility.
