Health risks posed by synthetic chemicals in our environment could potentially linger in our germline for generations.
A single exposure to a fungicide called vinclozolin during pregnancy increased the chance of disease for 20 generations of rats, a recent study found. The risk even seemed to rise, as the rats’ inherited health problems continued to worsen over time.
This study involved rodents, but such dramatic results in such a familiar mammalian model nonetheless hint at significant implications for humanity, the study’s authors suggest.
Research like this could help illuminate rising rates of many chronic diseases, for example, pointing to the possibility that someone’s diagnosis today could be rooted in an ancestor’s exposure to certain toxic substances decades earlier.
Beyond tracing the origins of disease, investigations into epigenetic transgenerational inheritance could inform new treatments, the researchers note. Epigenetics research has already identified disease biomarkers that could inspire novel treatment options.
“This study really does say that this is not going to go away,” says co-author Michael Skinner, a professor of biology at Washington State University. “We need to do something about it. We can use epigenetics to move us away from reactionary medicine and toward preventative medicine.”
Skinner helped identify epigenetic inheritance of disease risk two decades ago and has continued studying the phenomenon ever since.
It occurs when non-mutational changes occur to DNA in an organism’s germline, or the cellular lineage from which sperm and egg cells arise, affecting how critical genes are expressed.
As previous research has shown, inherited disease risk can eclipse the threat caused by direct exposure to the substance in question.
“Essentially, when a gestating female is exposed, the fetus is exposed,” Skinner says.
“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 another recent study, Skinner and his colleagues monitored rats for 10 generations after a single exposure to vinclozolin, which previous research has linked to potential health effects, including endocrine disruption and cancer.
The exposure boosted disease risk in the rats, they found, and this effect persisted through all 10 generations, raising questions about just how long it can last – and how bad it can get.
For the new study, the researchers continued tracking the same lineage of rats with ancestral vinclozolin exposure through 20 generations.
They found a similarly stubborn pattern of disease in the rats’ kidneys, prostate, testes, and ovaries, among other health effects. The severity also worsened in later generations, when large numbers of birthing mothers and their offspring began to die.
“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 says.
“By the 16th, 17th, 18th generations, disease became very prominent, and we started to see abnormalities during the birth process,” he adds. “Either the mother would die, or all the pups would die, so it was a really lethal sort of pathology.”
Previous research has found epigenetic changes in human germlines corresponding with findings from mammalian models, the researchers note.
Rates of chronic disease are also rising in humans, and while this research can only hint at a possible connection, the timing parallels the rising prevalence of pesticides and many other synthetic chemicals.
While 20 generations for rats can unfold in a few years, they may take half a millennium for humans. Nonetheless, Skinner is optimistic that epigenetic research can help identify new ways for medical science to intervene.
“In humans, we’ve actually got epigenetic biomarkers for about 10 different disease susceptibilities. It doesn’t say you have the disease now; it says 20 years from now, you’re potentially going to get this disease,” Skinner says.
“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,” he adds.
