Stressed dads may put kids at high diabetes risk: study

Fathers under psychological stress are more likely to have kids with high blood sugar compared to their unstressed counterparts, a new study in mice has found.

The study suggests that a male's life experience can be passed down through more than his genetic code alone. Researchers link this difference to an epigenetic change in the stressed dad's sperm - a change that they could prevent
by blocking the father's stress hormones.

Researchers confined male mice in plastic tubes for two hours a day, for two weeks straight, to induce stress. Afterwards, the animals' glucose levels were increased, but the mice gained weight more slowly and had increased levels of stress hormones called glucocorticoids in their blood.

These mice were then mated with females that had not been confined, and their resulting offspring had higher blood glucose than normal. "Paternal psychological stress can result in hyperglycemia in offspring in mice," said Xiaoying Li from
Shanghai Jiao Tong University School of Medicine in China.

The root of the increased blood sugar was in a gene called Sfmbt2. When a male mouse is immobilised daily in a plastic tube, the spike of glucocorticoids causes extra methyl groups to be added to the Sfmbt2 gene in his sperm.

These epigenetic marks do not affect the underlying DNA, but they do control how Sfmbt2 and an associated microRNA (the intronic microRNA-466b-3p) are expressed. The epigenetic reprogramming from stress, through glucocorticoids, was surprising, researchers said.

This epigenetic change in stressed fathers showed up in their offspring's livers. The intronic microRNA-466b-3p in Sfmbt2 is supposed to help regulate an enzyme called PEPCK, which controls sugar production in the liver. But when mammals reproduce, Sfmbt2 is turned off in the egg from the mother - meaning that offspring inherit their only working copy from the father's sperm.

And when the only functional Sfmbt2 gene carries these epigenetic tags, the intronic microRNA-466b-3p is silenced and can not keep watch over PEPCK as it normally would. The father's offspring then develop livers with too much PEPCK, causing their blood glucose to increase.

"It is potentially possible for our study to be translated into the treatment of hyperglycemia in human beings in the future," said Li. The findings were published in the journal Cell Metabolism.