Epigenetic Impacts

An epigenetic impact on an organism arises from changes in gene expression patterns, rather than direct, heritable mutations in DNA.

Mutations in DNA can occur during fetal development, as well as during any and all stages of life. Most mutations are quickly isolated by the body’s genetic-defense mechanisms, and are attacked and eliminated via a dizzying array of biological responses.  But a few escape the body’s best efforts to contain them, and become an established part of a person’s dividing cells.

This National Institutes of Health Graphic illustrates some of the mechanisms responsible for epigenetic changes in gene expression.

Some mutations have little or no impact on health outcomes, while others set the stage for, or even render inevitable, certain diseases and developmental anomalies.

But a mutation in a person’s DNA is not the only way that genetics can play a role in health and developmental outcomes.

Changes in when, why, and how fully genes are expressed can alter the ways that a person’s genes drive development, combat infection, or deal with nutritional deficits or excesses. Epigenetic disruption can impair neurological functions, as well as immune and reproductive systems, metabolic stability and responses to environmental cues. As a result, epigenetic disruptions can alter susceptibility to adult disease and chronic health problems.  For more on the implications of epigenetics, see this TED Ed video that does a great job of laying this complex science out clearly.

Studies in sophisticated, multi-generational animal models have reported significant epigenetic impacts following prenatal exposures to the two most widely applied herbicides in the U.S. and worldwide — atrazine and glyphosate.

A team based at Washington State University (WSU) reported that glyphosate induces heritable, epigenetic-driven adverse health outcomes in rats, but not in the first generation of pups born to an exposed dam. Kubsad et al. reported in a 2019 paper that the F2 offspring, or the grandpups, experienced heightened rates of prostrate disease, obesity, kidney disease, ovarian problems, and birth abnormalities, despite the absence of any further exposure to glyphosate in the mothers of the second-generation pups, or the pups themselves.

Another WSU based team reported in 2017 a similar set of adverse epigenetic impacts following prenatal exposure to atrazine. In the atrazine study by McBirney et al., the F2 pups experienced higher rates of testis disease, mammary tumors, early-onset puberty in males, and decreased bodyweight in females, when compared to control animals. Again, epigenetic impacts were observed despite the absence of any further exposure to atrazine to any study animals.

These recent studies reporting transgenerational epigenetic impacts were one of the main health concerns cited by the International Federation of Gynecology and Obstetrics in their 2019 statement calling for a “full global phase out” of glyphosate due to concerns about health impacts to women and children. 

The Heartland Study will deploy state-of-the-art genomic research tools in a search for markers of epigenetic change in the babies born to the mother-infant pairs enrolled in the study. We will then correlate markers of epigenetic changes in newborns and children as they develop, with observed developmental problems or health problems.

The Heartland Study will be the first clinically based study of humans exposed to herbicides with the potential to gain deeper understanding of whether, and to what extent epigenetic mechanisms are the root cause of certain adverse birth and developmental outcomes.

 

Key Science

Low Birthweight & Preterm Delivery

Developmental Effects

Birth Defects

Reproductive Impacts: Conception & Pregnancy

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