A single exposure to a common agricultural fungicide can have a much longer generational effect than previously understood, potentially impacting the health of offspring 20 generations later.
Researchers at Washington State University investigated the long-term effects of exposure to vinclozolin, a fungicide widely used on fruit crops to control mold and rot.
The study builds on 20 years of work by biologist Michael Skinner, who in 2005 first identified what is known as epigenetic transgenerational inheritance of disease. Unlike genetic mutations that change the DNA sequence, epigenetic changes change how genes are expressed and can be passed on through sperm and egg cells.
Professor Skinner, from the School of Biological Sciences, said: “This study really shows that this situation is not going away.” something needs to be done about it. We can use epigenetics to move away from reactionary medicine and toward preventive medicine. ”
In the latest study, scientists traced a lineage of rats whose ancestors were exposed to vinclozolin at carefully controlled doses during pregnancy. They tracked disease patterns over 20 generations. This is roughly equivalent to about 500 human years.
Previous studies had already shown that the risk of disease persists for 10 generations. The new study, which doubled in time, confirmed not only continued transmission of disease susceptibility, but also the spread of infection in later generations.
“The presence of disease was pretty much the same, but around the 15th generation we started to see an increase in disease status,” Skinner said. “By the 16th, 17th and 18th generation, the disease became very noticeable and we started seeing abnormalities in the birthing process. Either the mother died or all the puppies died, so it was a really fatal type of condition.”
The study also found changes in DNA methylation (chemical tags that influence gene activity) over multiple generations, along with increased sperm cell death in male rats. This suggests that when the germline is reprogrammed by environmental factors, the effects can become significantly stable and heritable.
“Basically, when a pregnant woman is exposed, the fetus is exposed,” Skinner explained. “And it also exposes the internal germline of the fetus. That exposure exposes the offspring to the potential effects of the exposure, and the offspring continue to experience the effects, and it continues. Once programmed into the germline, it’s as stable as a genetic mutation.”
Previous studies have found similar epigenetic changes in human germ cells to those seen in animal studies, suggesting that the findings may have relevance beyond the lab.
In theory, today’s environmental exposures could affect the health of our descendants centuries from now. With such a long gap between cause and effect, preventing harm becomes a major challenge.
Professor Skinner believes part of the solution may lie in epigenetic ‘biomarkers’ – measurable biological signals that can indicate the risk of developing a particular disease long before symptoms appear.
“In humans, we actually have epigenetic biomarkers of susceptibility to about 10 different diseases,” he said. “It’s not saying you have this disease now, it’s saying you could potentially have this disease 20 years from now.” There are a series of preventive medicine approaches that can be taken before the disease develops to delay or prevent the onset of the disease. ”