What your father ate before you were born could influence
your health

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.

Inspiration

“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.

Molecular carrier

“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.

Obesity

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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