There is increasing evidence that parents' lifestyle and the environment they inhabit even long before they have children may influence the health of their offspring. A current study, led by researchers from the Novo Nordisk Foundation Center for Basic Metabolic Research, sheds light on how.
Researchers in Associate Professor Romain Barrès' laboratory compared sperm cells from 13 lean men and 10 obese men and discovered that the sperm cells in lean and obese men, respectively, possess different epigenetic marks that could alter the next generation's appetite, as reported in the medical journal Cell Metabolism.
A second major discovery was made as researchers followed six men before and one year after gastric-bypass surgery (an effective intervention to lose weight) to find out how the surgery affected the epigenetic information contained in their sperm cells. The researchers observed an average of 4,000 structural changes to sperm cell DNA from the time before the surgery, directly after, and one year later.
"We certainly need to further examine the meaning of these differences; yet, this is early evidence that sperm carries information about a man's weight. And our results imply that weight loss in fathers may influence the eating behaviour or their future children," says Romain Barrès.
"Epidemiological observations revealed that acute nutritional stress, e.g. famine, in one generation can increase the risk of developing diabetes in the following generations," Romain Barrès states. He also referenced a study that showed that the availability of food in a small Swedish village during a time of famine correlated with the risk of their grandchildren developing cardiometabolic diseases.
The grandchildren's health was likely influenced by their ancestors' gametes (sperm or egg), which carried specific epigenetic marks -- e.g. chemical additions to the protein that encloses the DNA, methyl groups that change the structure of the DNA once it is attached, or molecules also known as small RNAs. Epigenetic marks can control the expression of genes, which has also been shown to affect the health of offspring in insects and rodents.
"In our study, we have identified the molecular carrier in human gametes that may be responsible for this effect," says Barrès.
By detecting differences in small RNA expressions (where the function is not yet determined) and DNA methylation patterns, the researchers have proven that weight loss can change the epigenetic information men carry in their spermatozoa. In other words, what is transmitted in the father's sperm can potentially affect the development of a future embryo and, ultimately, it can shape the child's physiology.
"We did not expect to see such important changes in epigenetic information due to environmental pressure," says Barrès. "Discovering that lifestyle and environmental factors, such as a person's nutritional state, can shape the information in our gametes and thereby modify the eating behaviour of the next generation is, to my mind, an important find," he adds.
If we consider it in an obesity context, a worldwide heritable metabolic disorder which is sensitive to environmental conditions (diet and physical activity) the discovery that weight loss in fathers-to-be potentially affects the eating behaviour of their offspring is ground-breaking.
"Today, we know that children born to obese fathers are predisposed to developing obesity later in life, regardless of their mother's weight. It's another critical piece of information that informs us about the very real need to look at the pre-conception health of fathers" says Ida Donkin, MD and one of the lead authors of the paper. She continues, "And it's a message we need to disseminate in society."
"The study raises awareness about the importance of lifestyle factors, particularly our diet, prior to conception. The way we eat and our level of physical activity before we conceive may be important to our future children's health and development," says Soetkin Versteyhe, co-first author of the paper.
It is still early days in this field of research, but the study disrupts the current assumption that the only thing our gametes carry is genetic information, and there is nothing we can do about it. Traits that we once thought were inevitable could prove modifiable, and what we do in life may have implications not only for our own health but also the health of our children and even our grandchildren. This work opens up new avenues for investigations of possible intervention strategies to prevent the transmission of disorders such as obesity to future generations.
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Primary Resource:Ida Donkin, Soetkin Versteyhe, Lars R. Ingerslev, Kui Qian, Mie Mechta, Loa Nordkap, Brynjulf Mortensen, Emil Vincent R. Appel, Niels Jørgensen, Viggo B. Kristiansen, Torben Hansen, Christopher T. Workman, Juleen R. Zierath, Romain Barrès. Obesity and Bariatric Surgery Drive Epigenetic Variation of Spermatozoa in Humans.Cell Metabolism, 2016; (in press) DOI: 10.1016/j.cmet.2015.11.004