In the last few decades, researchers have come to a better understanding of how certain diseases may be inherited epigenetically in humans, meaning they are passed down not through DNA sequences but through changes in gene expression. To help add to the body of work that proves this idea, the National Institute of Environmental Health Sciences has awarded a 5-year grant to a team of researchers including Ulrike Luderer, MD, PhD, professor of Environmental & Occupational Health at UC Irvine Public Health.
Specifically, the study will focus on a type of virus that has becomes incorporated into our DNA, a human endogenous retrovirus (HERV) called HML-2, which is usually silenced in normal cells, except for temporary activation in normal human primordial germ cells, the cells that will become sperm or eggs in males and females, respectively. This project will test the hypothesis that a trigger, such as exposure to environmental toxicants can cause HML-2 reactivation in germ cells and thereby increase cancer risk in the next generation.
As the lead investigator for a sub-award under the main grant, Luderer will utilize “humanized” mice that carry a human HML-2 locusto prove the study’s hypothesis that environmental toxicants (like pesticides and combustion products) might impair the silencing of HML-2 in germ cells.
Our study is uncovering yet another interference wherein a pregnant women’s exposure to toxicants may increase the child’s susceptibility to diseases like cancer later in life, highlighting the importance of avoiding harmful chemicals to protect both immediate and future health.”
– Ulrike Luderer, MD, PhD
Luderer’s lab will expose pregnant “humanized” female mice to environmental toxicants and harvest germ cells from the ovaries and testes of developing embryos. These germ cells will be tested for activation and silencing of the HML-2 locus. Activation possibly contributes to the development of cancers like breast cancer and melanoma in the next generation.
The outcome of this project may create a novel paradigm focusing on the toxicological importance of HML-2 as an inherited epigenetic vehicle, linking exposure of pregnant women to toxicants and cancer risk in the subsequent generation. These new insights are crucial for public health efforts to mitigate exposure to environmental toxicants not only among pregnant women but also the community-at-large.
“Harmful exposure to environmental toxicants is more common than many realize, and we are continually discovering that such exposures interfere with critical developmental processes in the embryo and fetus, causing birth defects, developmental delays, and long-term health issues,” Luderer said. “Our study is uncovering yet another interference wherein a pregnant women’s exposure to toxicants may increase the child’s susceptibility to diseases like cancer later in life, highlighting the importance of avoiding harmful chemicals to protect both immediate and future health.”
The Principal Investigator of this study is Toshihiro Shioda, MD, PhD, from Massachusetts General Hospital. The administrating institute is the National Institute of Environmental Health Sciences under the study section called Environmental Determinants of Disease.
