By BONNIE PRESCOTT, Beth Israel Deaconess Medical Center Staff
Heredity and genetics determine a number of key traits in offspring: DNA from mother and father determine hair color, eye color and height, for example. When genes are mutated, or damaged, these mutations can change the DNA code and increase a person’s likelihood of developing certain diseases.
But independent of hereditary changes caused by DNA mutations, investigators are studying how environmental factors, such as the amount or type of food a woman consumes during pregnancy or her exposure to stress or toxins, might influence her offspring’s health. Importantly, these environmental influences appear to extend far beyond infancy into adulthood — and even seem to be passed from one generation to the next. Known as epigenetics, this field is now a major focus of research, including a priority project of the National Institutes of Health (NIH).
“The concept that maternal health impacts the fetus in terms of later development is something that we have innately understood for a long time, but having some scientific explanations on the molecular and genetic levels is not only interesting but may validate some of these thoughts,” explains Dr. Karen O’Brien, a specialist in maternal-fetal medicine at BIDMC. “We’re always trying to encourage our pregnant patients to lead healthy lifestyles but as epigenetics continues to reveal new information, we may need to extend this counseling to the preconception time frame and even counsel fathers to eat healthy and avoid stress and toxic exposures.”
Researchers at BIDMC are examining epigenetics from several vantage points, including looking at changes that take place at the cellular level in obesity and diabetes and assessing the role that epigenetics may play in premature birth.
Epigenetics and Insulin Resistance
Dr. Evan Rosen, a researcher in BIDMC’s Division of Endocrinology, Diabetes and Metabolism, has been studying the role of epigenetics in the development of insulin resistance, a precursor to Type 2 diabetes.
“Epigenetic modifications refer to changes in the structure of DNA, but are fundamentally different than mutations that change the DNA sequence. Epigenetic alterations affect how DNA is folded and can have major effects on which genes are being turned on or off,” says Rosen. “We and others have looked at the risk of developing diabetes or obesity in animal models of disease through a process known as fetal programming, which centers on nutritional exposures in utero,” he adds.
“Whether a fetus has received too few or too many nutrients from the mother can lead to the development of obesity or diabetes in adulthood and this, in turn, can be passed along to the next generation,” says Rosen. “There is a lot of evidence that insulin resistance can be passed on this way and this type of intergenerational event almost certainly develops in the nucleus, where the DNA blueprint is stored.”
As he further explains, findings in animal studies have shown that mice born to mothers that were fed a low-calorie diet were smaller at birth and had a slower metabolism than mice born to the mothers that were fed a regular diet. But, over time, these small birth-weight animals eventually become overweight and prone to develop diabetes.
“It is as if these mouse pups learned in the uterus that they would be born into a food-restricted environment,” says Rosen. “This trains the genome in some way to promote calorie storage.” When, instead, food is plentiful, the mice grow obese and insulin resistant. These animal studies suggest that these effects may persist in DNA for generations, and epidemiologists are investigating data that indicate that the same process might be working in humans.
Epigenetics and Premature Birth
Dr. Heather Burris, a neonatologist at BIDMC, is now conducting a large epidemiological study to find out if epigenetic changes in a mother’s cervical cells play a role in premature births. Premature delivery is more common among poor and minority populations, and through epigenetics, researchers may be able to explain why this is the case.
Her previous work has suggested that differences in DNA methylation, a process that can turn genes off and prevent the production of proteins, may be associated with length of gestation. “Currently, we just don’t know which patients are going to deliver early,” says Dr. Burris. “We’re hoping that epigenetic markers will help us do a better job of understanding who may be at risk so that we can intervene.”
Epigenetics, she adds, has the potential to help us better understand and address some of our major public health concerns, including not only preterm birth, but also obesity, diabetes and asthma.
Disease Prevention Starts Early
“We look at pregnancy as a great teaching time,” says Hope Ricciotti, MD, Chair of the Department of Obstetrics and Gynecology at BIDMC. “It is a time when women will quit smoking, start exercising, and start taking better care of themselves because they are doing it for two. Research is revealing that diet and other factors that a fetus is exposed to in utero can have important health effects later in life. Epigenetics is an adaptive measure to ensure survival in various environments, and we want patients to understand that disease prevention starts early – even before birth.”
Above content provided by Beth Israel Deaconess Medical Center. For advice about your medical care, consult your doctor.
Posted May 2015