OBESE male mice tend to sire unhealthy offspring. And it seems diet is to blame, causing tiny changes in sperm that may lead to metabolic disorders in mouse pups. The discovery brings us closer to understanding how lifestyle choices affect the health of future generations.
The effects of diet and smoking become imprinted onto DNA via chemical modifications that regulate gene activity and protein production within a cell.
Such "epigenetic" changes were thought to be reset in sperm because the DNA in the nucleus opens up and is repackaged before and after fertilisation. This process was thought to wipe the epigenetic slate clean.
Now Maria Ohlsson Teague and Michelle Lane at the University of Adelaide, Australia, have shown that mice brought up on a bad diet have offspring that are prone to insulin resistance, suggesting that epigenetic changes persist in some regions of sperm cells.
To investigate, the team screened mouse sperm for tiny bits of genetic material that switch off protein production. They identified 21 of these microRNAs that were expressed differently in the sperm of mice fed on a high fat diet compared with those on a healthy diet.
The pair used a database of known microRNAs to predict the effect of the altered markers. The top biological networks likely to be affected were associated with embryo and sperm development, and metabolic disorders.
The large amounts of fat around the testes of obese mice, "could alter the environment and encourage epigenetic changes", says Teague, who presented the results at the 14th World Congress on Human Reproduction in Melbourne, Australia, this month.
In the future, it may be possible to screen sperm during IVF or block unwanted epigenetic changes with drug therapy, says Teague. "We prefer to encourage healthy lifestyles," she adds.
David de Kretser at the University of Melbourne says the work is "fascinating". Now the key is to understand when all this is happening, he says.
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