by Washington State University

DMR identification. The number of DMRs found using different P-value cutoff thresholds. The All-Window column shows all DMRs. The Multiple Window column shows the number of DMRs containing at least two nearby significant windows (1 kb each). The number of DMRs with the number of significant windows (1 kb per window) at a P-value threshold of P < 1e-04 for DMR is bolded. Credit: Environmental Epigenetics (2023). DOI: 10.1093/eep/dvad006

While exposure to a single substance like DDT has been shown to create inherited disease susceptibility, a recent study in animals found exposure to multiple different toxicants across generations can amplify those health problems.

In the study, published in the journal Environmental Epigenetics, an initial generation of pregnant rats was exposed to a common fungicide, then their progeny to jet fuel and the following generation to DDT. When those rats were then bred out to a fifth unexposed generation, the incidence of obesity as well as kidney and prostate diseases in those animals were compounded, rising by as much as 70%.

Researchers also found that their epigenetics, molecular processes independent of DNA that influence gene expression, were also greatly altered.

"We looked at multiple-generation exposures because these types of things are going on routinely, and previous research has only looked at single exposures," said Michael Skinner, a WSU biology professor and the study's corresponding author. "We found that if multiple generations get different exposures, then eventually there's an amplification or compounded effect on some diseases."

The study did show that for other diseases, those associated with the ovaries and the testes, the incidence rose in the first generation of progeny but appeared to plateau with the additional generational exposures.

Skinner and his colleagues also conducted epigenetic analysis of each generation of the animals, finding that the toxicant exposures shifted their entire epigenetics dramatically. Along with changes to genes themselves, inherited epigenetics which influence gene expression, are considered to have a significant impact on evolution.

"When we made the comparisons with different generations, we did not find a lot of overlap in epigenetics. In other words, every time each generation had a new exposure, it appeared to reprogram the whole epigenome," Skinner said.

While the study does not exactly mimic what may have happened to human generations, people in the U.S. have potentially been exposed to these particular toxicants at different times. The authors note a likely sequential exposure over human generations might involve an exposure to DDT which was widely used in the 1950s, then plastics in the 1970s, followed by many modern herbicides still in use today.

The study provides evidence that multiple toxicant exposures of past human generations likely had a compounded impact on grandchildren and great-grandchildren. Knowing about these possible impacts can help people and doctors address potential diseases before they develop, Skinner said.

Researchers including Skinner's lab at WSU have been working to identify epigenetic biomarkers for inherited health conditions in humans including for obesity, autism and pre-term birth.

"We need to know to what degree our past generations activities that have affected us," Skinner said. "We cannot necessarily fix this problem, but it's important to know that it happened so that we can try to better treat potential health problems through preventative medicine."

More information: Eric E Nilsson et al, Multiple generation distinct toxicant exposures induce epigenetic transgenerational inheritance of enhanced pathology and obesity, Environmental Epigenetics (2023). DOI: 10.1093/eep/dvad006

Provided by Washington State University