Research indicates that exposure to a specific fungicide has lasting effects on gene expression in rats for at least 20 generations. This exposure appears to elevate the likelihood of offspring facing kidney disease, obesity, or complications during childbirth, according to one of the longest studies on this topic in mammals.
There’s growing evidence that certain environmental factors, including chemicals, can lead to inherited changes that don’t modify the organism’s DNA directly. These alterations to chemical markers on DNA happen in germ cells, which are then transmitted to future generations. Yet, most research so far has concentrated on the generations that were directly exposed, overlooking the subsequent ones.
A recent investigation led by Michael Skinner from Washington State University examined the effects of the fungicide vinclozolin on an original generation of rats, extending over 20 generations. The team observed that those with ancestors exposed to vinclozolin exhibited increased rates of sperm cell mortality and complications in births, such as higher maternal and offspring mortality, compared to non-exposed rats or those from earlier generations.
Anthony Hannan, an epigenetics researcher, described the results as “quite shocking.”
However, the implications for humans remain uncertain. While there are documented cases of epigenetic changes passed through generations—for instance, descendants of people who experienced famine showing increased diabetes risks—more research is needed to clarify whether specific health conditions in people can be traced back to ancestral exposures, according to Hannan.
Still, these findings highlight the importance of being cautious about air quality and the chemicals we allow into our environment, as noted by Razia Zakarya, another epigenetics researcher. “Seeing this kind of accumulation of epigenetic markers leading to health issues much later on is pretty alarming,” she commented.
The use of vinclozolin in agriculture has diminished over the last quarter-century and it is banned in several countries, including Australia and those in the European Union.
Indirect Effects
Skinner and his research team initiated their experiments in 2017. They injected pregnant rats with vinclozolin and a solvent called DMSO, then bred these rats with non-exposed ones over 23 generations, which is, in human terms, roughly equivalent to 500 years. The initial pregnant rat and its direct descendants were classified as directly exposed, while the following 20 generations were considered ancestrally exposed. A control group received only DMSO and was bred for four generations.
Using next-generation sequencing, the researchers identified variations in DNA methylation within the rats’ genomes. Later generations showed an increase in the number of regions with these differences compared to control rats, indicating that the epigenetic changes persist over generations.
Upon examination of the rats’ kidneys, reproductive organs, and other areas, the team discovered a rise in diseases affecting these organs across subsequent generations. For instance, in the twentieth generation, all 11 rats with paternal exposure displayed ovarian abnormalities, contrasting with 11 out of 19 control rats. More severe health issues like obesity and kidney disease were also recorded in the exposed rats, suggesting that DNA methylation disrupts normal development and functioning of organs.
The researchers additionally found higher rates of complications during births in ancestrally exposed females, including maternal fatalities during labor or offspring deaths in utero. Birth success rates ranged from 20% to 70% in later generations compared to controls.
