In last week’s blog post, we explained the variety of molecular mechanisms that control gene expression and make up your epigenome. There is a lot scientists still don’t know about the complex machinations of your epigenome, and there’s even more they don’t know about how those changes respond to the environment and get passed down through generations. There is mounting evidence suggesting that some epigenetic changes are inherited, providing a pathway for behaviors, environments, and traumas to be passed on through generations. But how does this inheritance take place? And what could it mean for our health and the health of our grandchildren?
When we talk about environmental inheritance, we are really talking about two different ways the environment can impact how the epigenome is inherited. Multigenerational epigenetic inheritance refers to environmental exposures that directly affect a developing embryo or the sperm/egg cells that formulate an embryo. These exposures directly interact with both the parent and child simultaneously—even long before the child is conceived. And when the environmental exposure affects a developing embryo, it directly interacts with the mother, the child, and the grandchild (through in-utero changes to the cells that will eventually become the child’s sperm and egg cells). Often, we are more interested in transgenerational epigenetic inheritance, which refers to changes in the epigenome that are passed on to cells that had no contact with the original environmental exposure. So if your grandfather ran behind the insecticide truck as a kid, those chemicals may have directly changed the epigenome of one of your parents (by interacting with the germline cells that became your grandfather’s sperm cells). That’s multigenerational epigenetic inheritance. If those changes persist for another generation and affect your genes, then that would be transgenerational epigenetic inheritance.
For a while, scientists assumed that transgenerational epigenetic inheritance couldn’t occur because of a phenomenon known as epigenetic reprogramming. When an embryo first forms, all of its DNA comes pre-tagged with the epigenetic markers from the egg and sperm cells that formed it. But the genes that need to be turned on in germline cells are very different than the genes that need to be turned on in the heart, the lungs, or the liver. In order for embryonic cells to differentiate into all of the different cell types necessary for a functioning infant, they first need to erase most of the epigenetic tags, leaving blank slate cells that can be adapted into any type of cell necessary. But, in mammals, approximately 1% of embryonic genes keep their original epigenetic tags in a process called imprinting. Imprinting allows the cell to control whether the maternal or paternal copy of a gene is expressed. Scientists are still working to understand how environmental exposures may interact with imprinting patterns to facilitate epigenome inheritance. But there is empirical evidence suggesting transgenerational epigenetic inheritance does happen to some extent.
Epigenome inheritance is often studied in mice and rats, which are useful model organisms scientists can easily track for multiple generations. For example, scientists have seen multigenerational epigenetic inheritance in the genes that control fur color, where chemicals in a pregnant mother’s diet changed the fur color of their offspring by switching off certain genes. But these changes don’t appear to persist transgenerationally. A different study found that when pregnant rats were exposed to a fungicide used in agriculture, their great-grandchildren had changes in their epigenome correlating with reproductive abnormalities like decreased sperm motility. Going back to your grandfather who ran behind insecticide trucks, a study of pregnant rats exposed to DDT—an insecticide that was banned in the U.S. in 1972—found that the chemical caused changes in the epigenomes of their great-grandchildren that were correlated with the development of obesity. Rats exposed to nicotine had great-grandchildren at higher risk for asthma; mice exposed to chronic social stress had great-granddaughters with higher social anxiety; and mice exposed to BPA had great-grandchildren with decreased social interactions and altered brain chemistry. Altogether these animal studies present robust evidence that environmental exposures can impact health transgenerationally through inherited changes in the epigenome.
It’s much harder to study transgenerational epigenetic inheritance in humans because it requires tracking large study populations across multiple generations. And because it’s impossible to precisely control the conditions of a person’s life, it can be harder to pin down exactly what causes these generational changes. Preliminary evidence has indicated that if a grandparent is exposed to sudden bouts of famine, it puts their grandchild at higher risk for dying of heart disease. A study of mothers in Norway found that smoking while pregnant put their grandchildren at higher risk for asthma. There are several studies that look at the epigenetic effects of extreme trauma, including studies of Holocaust survivors and their descendants. But these studies have only been able to find limited evidence for epigenetic inheritance of stress in humans. And it’s difficult to isolate epigenetics as the cause when there are so many other psychological and social factors underlying intergenerational trauma.
Despite the limitations of human epigenome inheritance studies, there is evidence that certain diseases are inherited epigenetically. For example, Prader-Willi syndrome and Angelman syndrome are both neurological disorders often caused by a mutation in chromosome 15. But studies have found that a subset of people with these disorders inherits them transgenerationally as the result of faulty imprinting in chromosome 15 during epigenome reprogramming. There is also preliminary evidence that epigenetic changes associated with cancer risk could be inherited transgenerationally. As we further decode the epigenome and its complex inheritance, we may reveal even more hidden links between environment and disease.
Science You Can Bring Home To Mom will be back in August with a brand new series! For now, check out last month’s series on biological sex and gender. Comment on this post or email me at contact@anyonecanscience.com to let me know what you think about this week’s blog post and tell me what sorts of topics you want me to cover in the future. And subscribe below for weekly science posts sent straight to your email!
