A single exposure to the fungicide vinclozolin during pregnancy can increase the risk of disease for at least 20 subsequent generations, according to a new study from Washington State University (WSU). The research, published this week in the Proceedings of the National Academy of Sciences, expands understanding of how environmental toxins can be passed down through alterations in reproductive cells.
The study tracked a lineage of rats whose pregnant ancestors were exposed to vinclozolin, a fungicide once widely used on crops including strawberries, raspberries, lettuce, and grapes. Researchers observed disease patterns across 20 generations, finding that disease susceptibility not only persisted but escalated in later generations.
“This study really does say that this is not going to go away,” said Michael Skinner, a professor in the School of Biological Sciences and founding director of the Center for Reproductive Biology at WSU. “We need to do something about it. We can use epigenetics to move us away from reactionary medicine and toward preventative medicine.”
Previous research, dating back to 2005, had already demonstrated the transmission of disease risk through 10 generations. The current study doubled that timeframe, revealing a concerning trend. Whereas the presence of disease remained relatively stable for the first 15 generations, researchers noted a significant increase in disease incidence around the 15th generation. By the 16th, 17th, and 18th generations, disease became “very prominent,” with severe birth abnormalities emerging.
“By the 16th, 17th, 18th generations, disease became very prominent and we started to see abnormalities during the birth process. Either the mother would die, or all the pups would die, so it was a really lethal sort of pathology,” Skinner said.
The research identified altered DNA methylation – a chemical process that affects gene activity – across multiple generations. Researchers also observed increased death of sperm cells in male rats. These findings suggest that once the germline—cells that give rise to sperm and eggs—is reprogrammed by environmental factors, the effects can become remarkably stable and heritable.
“Essentially, when a gestating female is exposed, the fetus is exposed,” Skinner explained. “And then the germline inside the fetus is also exposed. From that exposure, the offspring will have potential effects of the exposure, and the grand offspring and it keeps going. Once it’s programmed in the germline, it’s as stable as a genetic mutation.”
The study’s findings have implications for understanding rising rates of chronic disease in humans, suggesting that ancestral exposures to toxins may be a contributing factor. Researchers have found epigenetic changes in human reproductive cells that correspond with those observed in animal studies, indicating the potential relevance of these findings beyond the laboratory setting.
Skinner’s team is now exploring epigenetic “biomarkers” – measurable biological signals that could indicate a person’s risk of developing certain diseases years before symptoms appear. “In humans, we’ve actually got epigenetic biomarkers for about 10 different disease susceptibilities,” he said. “It doesn’t say you have the disease now, it says 20 years from now, you’re potentially going to secure this disease. There’s a whole series of preventative medicine approaches that can be taken before the disease develops to delay or prevent the disease from happening.”
