Spermatozoa from obese men carry a distinct epigenetic signature compared to lean men, in particular at genes controlling brain development and function. The sperm methylome is dynamically remodeled after gastric-bypass-induced weight loss, notably at gene regions implicated in the central control of appetite. [Donkin et al., Cell Metabolism]
Spermatozoa from obese men carry a distinct epigenetic signature compared to lean men, in particular at genes controlling brain development and function. The sperm methylome is dynamically remodeled after gastric-bypass-induced weight loss, notably at gene regions implicated in the central control of appetite. [Donkin et al., Cell Metabolism]

It may be just a matter of time before someone writes a book called “Lean Dad Fat Dad” in hopes of emulating the success of “Rich Dad Poor Dad,” a bestseller that summarized the financial life lessons that can be passed from generation to generation. “Lean Dad Fat Dad,” however, wouldn’t be about the behaviors that are determined by example, advice, and custom. Instead, it would be about sperm.

Sperm not only conveys genetic information, it also carries information about a father’s weight. And the information about weight, which is encoded epigenetically and in the patterns of small RNA expression, has the potential to tip developing offspring toward obesity.

Obesity has been known to be a heritable disorder, with the children of obese fathers having a high risk of becoming obese. Not all of this risk is genetic. Some of it is due to lifestyle or environmental factors, which can be reflected epigenetically. That is, factors such as obesity can affect the way genes are expressed.

Researchers at the University of Copenhagen decided to expand upon existing epigenetic studies, which have suggested that times of famine can leave epigenetic traces that last generations. One such study considered how a time of famine in a small Swedish village had generational health impacts. Essentially, parents who experienced nutritional stress ultimately had grandchildren who were more likely to develop cardiometabolic diseases.

The grandchildren's health was likely influenced by their ancestors' gametes (sperm or egg), which carried specific epigenetic marks, such as 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.

The study of the Swedish village and other such studies suggest that epigenetic marks can be persistent and have lasting impacts. But much about the nature of these marks remains elusive. What sort of marks, exactly, may occur in gametes? And how readily may these marks be altered in response to environmental pressures?

Early answers have been offered by the University of Copenhagen scientists. Led by Romain Barrès, Ph.D., these scientists compared sperm cells from 13 lean men and 10 obese men. Dr. Barrès’ team also followed six men before and one year after gastric-bypass surgery to find out how the surgery affected the epigenetic information contained in their sperm cells.

“Our results,” said Dr. Barrès, “imply that weight loss in fathers may influence the eating behavior or their future children.”

This assertion is based on work that appeared December 6 in the journal Cell Metabolism, in an article entitled, “Obesity and Bariatric Surgery Drive Epigenetic Variation of Spermatozoa in Humans.”

“Comprehensive profiling of the epigenome of sperm from lean and obese men showed similar histone positioning, but small noncoding RNA expression and DNA methylation patterns were markedly different,” the article’s authors wrote. “In a separate cohort of morbidly obese men, surgery-induced weight loss was associated with a dramatic remodeling of sperm DNA methylation, notably at genetic locations implicated in the central control of appetite.”

In the separate cohort, the researchers observed an average of 4,000 structural changes to sperm cell DNA from the time before the surgery, directly after the surgery, and one year later. More needs to be learned about what these differences mean and their effects on offspring, but it is early evidence that sperm carries information about a man’s health.

“Our research could lead to changing behavior, particularly preconception behavior of the father,” noted Dr. Barrès. “It is common knowledge that when a woman is pregnant she should take care of herself—not drink alcohol, stay away from pollutants, etc.—but if the implication of our study holds true, then recommendations should be directed toward men, too.”

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