A recent study from Washington State University has found that a single prenatal exposure to the fungicide vinclozolin can increase disease risk for up to 20 generations in rats. The research, published in the Proceedings of the National Academy of Sciences, suggests that inherited health problems may worsen many generations after the initial exposure.
The study was co-authored by Michael Skinner, a WSU biologist who has been researching "epigenetic transgenerational inheritance" for two decades. This concept refers to diseases being passed down through changes in reproductive cells rather than direct genetic mutations.
Skinner explained how exposure during pregnancy affects multiple generations: "Essentially, when a gestating female is exposed, the fetus is exposed," he said. "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."
In earlier work published last year, Skinner's team tracked 10 generations of rats after an initial vinclozolin exposure and observed persistent disease rates across those generations. The current study doubled this number to 20 generations and found similar patterns of disease affecting organs such as kidneys, prostate, testes, and ovaries. In later generations—starting around generation 15—the researchers noted increased disease severity and higher mortality during birth.
"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."
Skinner noted that they used conservative toxin dosages below typical human dietary exposures.
The paper’s authors include Eric Nilsson from WSU’s School of Biological Sciences; Alexandra A. Korolenko—now at Texas Tech University—as lead author; and Sarah De Santos from Skinner’s lab.
Skinner suggested these findings could help explain increasing rates of chronic diseases among humans—a trend that coincides with greater use of pesticides and other chemicals in agriculture over recent decades. According to data from U.S. Centers for Disease Control (CDC), more than three-quarters of Americans live with at least one chronic illness such as heart disease or cancer; over half have two or more conditions.
While epigenetic alterations seen in human reproductive cells align with results from animal studies on transgenerational inheritance patterns of disease risk across populations separated by hundreds of years (20 rat generations equals about 500 human years), identifying specific causes remains challenging due to long timeframes involved.
To address these risks proactively rather than reactively after symptoms develop later in life—which could be decades post-exposure—Skinner pointed out advances made possible by epigenetics research: "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."
