Obesity is a metabolic disorder resulting from behavioral and heritable causes. Children of obese fathers are at higher risk of developing metabolic disease later in life, independent of the body weight of their mother, supporting the notion that paternal factors contribute to the inheritance of obesity and obesity-related traits.
Previous studies show that the availability of food to people living in a small Swedish village during famine correlated with the risk of their grandchildren developing cardiometabolic diseases. The nutritional stress of the grandparents was likely passed down via epigenetic marks, these can be chemical additions on protein that wrap up DNA, methyl groups that change the structure of DNA once attached, or molecules called small RNAs. Epigenetic marks can control how genes are expressed, and this has also been shown to affect the health of offspring in insects and rodents. Therefore, the lab hypothesized that weight loss remodels the epigenetic signature of spermatozoa in human obesity. The current study is the first epigenetic mapping of spermatozoa in obese men and shows a distinct epigenome that characterizes human obesity.
The current study compared specific epigenetic marks in the sperm of lean and obese men. Results show that while no differences were seen in the proteins that wrap up DNA, there were variations between the participants’ small RNAs as well as methylation of genes associated with brain development and appetite. The group also followed 6 men undergoing weight-loss surgery to see how it affected their sperm. Data findings show that an average of 5,000 structural changes to sperm cell DNA were observed from the time before the surgery, directly after, and one year later. The researchers note that further studies are needed to investigate what these differences mean and their effects on offspring, with early evidence showing that sperm carries information about a man’s health.
The team surmise that their findings could lead to changing pre-conception behaviour of the father, for example staying away from alcohol and pollutants. For the future, the researchers state that to learn more about the epigenetic-offspring connection they plan to begin embryonic research to study epigenetic differences from the sperm of men with various degrees of body weight.
Source: Novo Nordisk Foundation Center for Basic Metabolic Research
