A single exposure to a common agricultural fungicide may echo through the generations far longer than previously understood – potentially affecting the health of descendants 20 generations later.
Researchers from Washington State University examined the long-term effects of exposure to vinclozolin, a fungicide widely used on fruit crops to control mould and rot.
The study builds on two decades of work by biologist Michael Skinner, who first identified what is known as epigenetic transgenerational inheritance of disease in 2005. Unlike genetic mutations, which alter DNA sequences, epigenetic changes modify how genes are expressed – and can be passed down through sperm and egg cells.
Skinner, a professor in the School of Biological Sciences said: ‘This study really does say that this is not going to go away. We need to do something about it. We can use epigenetics to move us away from reactionary medicine and toward preventative medicine.’
In the latest research, scientists followed a lineage of rats whose pregnant ancestor had been exposed to vinclozolin at a carefully controlled dose. They tracked disease patterns across 20 generations – roughly equivalent to about 500 years in human terms.
Earlier work had already shown that disease risk persisted through 10 generations. Doubling the timeframe, the new study confirmed not only continued transmission of disease susceptibility, but an escalation in later generations.
‘The presence of disease was pretty much staying the same, but around the 15th generation, what we started to see was an increased disease situation,’ Skinner said. ‘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.’
The study also revealed altered DNA methylation – a chemical tag that affects gene activity – across multiple generations, along with increased death of sperm cells in male rats. This suggests that once the germline is reprogrammed by environmental factors, the effects can become remarkably stable and heritable.
‘Essentially, when a gestating female is exposed, the foetus is exposed,’ Skinner explained. ‘And then the germline inside the foetus 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.’
Previous research has found similar epigenetic changes in human reproductive cells to those seen in animal studies, suggesting the findings may be relevant beyond the lab.
In theory, an environmental exposure today could affect the health of descendants centuries into the future. With such a long gap between cause and effect, preventing harm becomes a major challenge.
Skinner believes part of the solution may lie in epigenetic ‘biomarkers’ – measurable biological signals that can indicate a person’s risk of developing certain diseases long 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 get 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.’
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