Summary: A single exposure to a common fungicide during pregnancy can haunt a family line for 20 subsequent generations, according to a staggering new study. The research found that health problems\u2014including kidney, prostate, and reproductive issues\u2014not only persisted but actually worsened centuries later in \u201chuman time.\u201d<\/p>\n
By the 15th generation, the pathology became lethal, with high rates of death during birth for both mothers and offspring. This discovery of \u201cepigenetic transgenerational inheritance\u201d suggests that many modern chronic diseases may be rooted in the environmental exposures of ancestors who lived hundreds of years ago.<\/p>\n
Key FactsThe 20-Generation Span: Disease risk from a single toxic exposure remains stable for at least 20 generations, equivalent to roughly 500 years in humans.Lethal Progression: While disease rates stayed steady for the first 14 generations, they surged around the 15th, leading to severe abnormalities and death during the birth process.Germline Programming: Once a toxin alters the reproductive cells (sperm or egg), the change becomes as stable and permanent as a genetic mutation.Low-Dose Impact: The study used conservative toxin levels\u2014lower than what the average person might consume in their daily diet.Preventative Potential: Despite the daunting timeline, researchers have identified epigenetic biomarkers that can predict these disease susceptibilities 20 years before they develop, offering a window for preventative medicine.<\/p>\n
Source: Washington State University<\/p>\n
A single exposure to a toxic fungicide during pregnancy can increase the risk of disease for 20 subsequent generations \u2014 with inherited health problems worsening many generations after exposure.<\/p>\n
Those are the findings of a new Washington State University study of rats that expands the understanding of how long the intergenerational effects of toxic exposure may last, as they are passed down through alterations in reproductive cells.<\/p>\n
The study,\u00a0published this week in the\u00a0Proceedings of the National Academy of Sciences, was co-authored by WSU biologist Michael Skinner, who has been studying this \u201cepigenetic transgenerational inheritance\u201d of disease for two decades.<\/p>\n
The research has implications for deciphering rising disease rates among humans, Skinner said, suggesting that the reason someone has cancer today may be rooted in an ancestor\u2019s exposure to toxins decades earlier. On the other hand, epigenetics research has also unearthed potential treatments by identifying measurable biomarkers for diseases that could eventually spur preventative treatments.<\/p>\n
\u201cThis study really does say that this is not going to go away,\u201d said Skinner, a professor in the School of Biological Sciences and founding director of the Center for Reproductive Biology. \u201cWe need to do something about it. We can use epigenetics to move us away from reactionary medicine and toward preventative medicine.\u201d<\/p>\n
Skinner first identified the epigenetic inheritance of disease in 2005 and has published scores of papers since. The effects are transmitted through alterations in sperm and egg cells\u2014the germline\u2014and past studies have shown that the inherited disease incidence can be greater than that arising from direct exposure to toxins.<\/p>\n
\u201cEssentially, when a gestating female is exposed, the fetus is exposed,\u201d he said. \u201cAnd 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\u2019s programmed in the germline, it\u2019s as stable as a genetic mutation.\u201d<\/p>\n
Recently, Skinner\u2019s lab has been trying to determine how long those effects last and whether the disease risk changes over the generations.<\/p>\n
In a study published late last year, Skinner\u2019s team looked at 10 generations of rats following an initial exposure of vinclozolin, a fungicide used primarily in fruit crops to control blight, mold and rot. The heightened prevalence of disease persisted through those generations.<\/p>\n
The current paper, published in the\u00a0Proceedings of National Academy of Sciences, doubled the number of generations studied, showing a similar persistence of disease in the kidneys, prostate, testes and ovaries, as well as other health effects. What\u2019s more, starting in later generations, mothers and offspring began to die in large numbers during the birth process.\u00a0<\/p>\n
\u201cThe presence of disease was pretty much staying the same, but around the 15th\u00a0generation, what we started to see was an increased disease situation,\u201d Skinner said. \u201cBy 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.\u201d<\/p>\n
Skinner said he scaled the dosage of the toxin conservatively, at a level below what the average person might consume in their diet.<\/p>\n
The paper was co-authored by Eric Nilsson, a research professor in the School of Biological Sciences; Alexandra A. Korolenko, a previous graduate student and now postdoctoral researcher at Texas Tech University who was the lead author; and Sarah De Santos, an undergraduate research assistant in the Skinner laboratory.<\/p>\n
Skinner said epigenetic disease inheritance could help explain the rising rates of chronic disease in humans, an increase that paralleled the rising use of pesticides, fungicides and other environmental chemicals in agriculture and other industries. More than three-quarters of Americans now deal with a chronic disease such as heart disease, cancer or arthritis, and more than half have two diseases, according to the U.S. Centers for Disease Control.<\/p>\n
Research by Skinner and others has found epigenetic alterations in human germlines that correspond with mammal studies, and the increased incidence of human disease tracks with the transgenerational results found in animal studies.<\/p>\n
The scale of the time period involved is daunting. Twenty generations in rat populations cover a few years; in human beings, it\u2019s more like 500. With such a long stretch of time between the potential cause and effect, how might the impacts of the exposures be mitigated?<\/p>\n
Skinner pointed to another product of epigenetic research as a possible answer: the discovery of epigenetic biomarkers that predict susceptibility to specific diseases. Developing the use of epigenetic biomarkers to drive preventative treatments in humans could offer a valuable strategy for offsetting the long-term effects.<\/p>\n
\u201cIn humans, we\u2019ve actually got epigenetic biomarkers for about 10 different disease susceptibilities,\u201d he said.<\/p>\n
\u201cIt doesn\u2019t say you have the disease now, it says 20 years from now, you\u2019re potentially going to get this disease. There\u2019s a whole series of preventative medicine approaches that can be taken before the disease develops to delay or prevent the disease from happening.\u201d<\/p>\n
Key Questions Answered:Q: Does this mean I\u2019m doomed by what my great-great-grandparents ate?<\/p>\n
A: It means your baseline risk might be higher, but it\u2019s not a destiny. The study highlights that while the \u201cprogramming\u201d is there, we are now discovering biomarkers that can tell us which diseases we are susceptible to decades before they show up. This turns \u201creactionary\u201d medicine into \u201cpreventative\u201d medicine.<\/p>\n
Q: Why did the disease get worse after 15 generations?<\/p>\n
A: This is the most shocking part of the study. It suggests that epigenetic changes don\u2019t just \u201cfade out\u201d; they can reach a tipping point where the accumulated cellular stress becomes lethal. In the rat models, this manifested as a \u201clethal pathology\u201d during birth.<\/p>\n
Q: What was the specific toxin used?<\/p>\n
A: The researchers used vinclozolin, a fungicide commonly used on fruit crops to control rot and mold. They purposefully used a dose scaled below average human dietary consumption to show how sensitive the germline is to environmental chemicals.<\/p>\n
Editorial Notes:This article was edited by a Neuroscience News editor.Journal paper reviewed in full.Additional context added by our staff.About this epigenetics research news<\/p>\n
Author: Shawn Vestal<\/a>
Source: Washington State University<\/a>
Contact: Shawn Vestal \u2013 Washington State University
Image: The image is credited to Neuroscience News<\/p>\n