Toxic Fungicide Exposure: Health Risks Persist for 20 Generations | WSU Study

A single exposure to a toxic fungicide during pregnancy can have lasting health consequences for up to 20 generations, according to a new Washington State University (WSU) study. The research, published this week in the Proceedings of the National Academy of Sciences, expands our understanding of how environmental toxins can be passed down through generations via alterations in reproductive cells.

The study, led by WSU biologist Michael Skinner, who has been researching “epigenetic transgenerational inheritance” for two decades, suggests that the roots of some modern diseases may lie in ancestral exposures to toxins. While daunting, this research also points toward potential preventative treatments by identifying measurable biomarkers for disease susceptibility.

“This study really does say that this is not going to go away,” said Skinner, a professor in the School of Biological Sciences and founding director of the Center for Reproductive Biology. “We need to do something about it. We can use epigenetics to move us away from reactionary medicine and toward preventative medicine.”

How Epigenetic Inheritance Works

Skinner first identified the epigenetic inheritance of disease in 2005. The effects are transmitted through alterations in sperm and egg cells – the germline – and previous studies have shown that the inherited disease incidence can be greater than that arising from direct exposure to toxins. Essentially, exposure during pregnancy affects not only the developing fetus but also the germline cells within that fetus. These altered germline cells then pass on the potential for disease to subsequent generations.

“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 Rat Study: Vinclozolin and Multi-Generational Effects

The recent WSU study focused on the fungicide vinclozolin, commonly used in fruit crops to control blight, mold, and rot. Skinner’s team examined 10 generations of rats following initial exposure to the fungicide, observing a persistent increase in disease prevalence. The current study doubled that timeframe, examining 20 generations and finding a similar persistence of disease in the kidneys, prostate, testes, and ovaries, along with other health effects.

Interestingly, the researchers observed a concerning trend starting around the 15th generation. Disease incidence remained relatively stable until this point, but then began to escalate. By the 16th, 17th, and 18th generations, disease became more prominent, and there was a significant increase in mortality during the birthing process.

“The presence of disease was pretty much staying the same, but around the 15^th 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 dosage of vinclozolin used in the study was intentionally conservative, Skinner noted, set below levels typically consumed by humans through their diet.

Implications for Human Health

The findings have significant implications for understanding the rising rates of chronic diseases in humans, which have paralleled the increased use of pesticides, fungicides, and other environmental chemicals in agriculture, and industry. According to the U.S. Centers for Disease Control, more than three-quarters of Americans now live with a chronic disease, such as heart disease, cancer, or arthritis, and over half have two or more.

Skinner and other researchers have found epigenetic alterations in human germlines that correspond with the animal studies, and the increased incidence of human disease appears to track with the transgenerational results observed in animals.

From Reactionary to Preventative Medicine

Given the long timeframe involved – 20 generations in rats equates to roughly 500 years in humans – mitigating the effects of past exposures presents a considerable challenge. However, Skinner suggests that epigenetic research offers a potential pathway forward: the discovery of epigenetic biomarkers that can predict susceptibility to specific diseases.

“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.”

This research underscores the importance of considering the long-term, intergenerational consequences of environmental exposures and highlights the potential of epigenetics to shift the focus from treating disease to preventing it.