Damaging effects of obesity on fertility reversed

In a breakthrough, researchers have found how to reverse the damage obesity causes to a woman's fertility and her offspring.

Researchers at the University of Adelaide said the findings in mice have major implications for the future of fertility research.

"It's now well established that obesity in females leads to very serious fertility problems, including the inability to conceive," said lead author associate professor Rebecca Robker from the University's Robinson Research Institute.

"Obesity can also result in altered growth of babies during pregnancy, and it permanently programmes the metabolism of offspring, passing the damage caused by obesity from one generation to the next.

"In our laboratory studies, we've been able to unravel a key mechanism that leads to this multi-generational damage, and we've found a way to stop it happening," Robker said.

The research team found that obesity leads to a particular stress response that causes
damage to the mitochondria, which are critical energy-producing 'organs' within living cells.

"All of the mitochondria in our bodies come from our mother. If the mother is obese, this produces stresses that lead to reduced transmission of mitochondria to the offspring," Robker said.

"We found that the eggs of such mothers lead to heavier-than-normal foetuses with greatly reduced amounts of mitochondrial DNA and other obvious signs of damage," she said.

"Once we had identified the type of stress involved, we used compounds known to alleviate that stress in the cells. In particular, we were interested in compounds that are also being tested in diabetes clinical trials," Robker said.

"These compounds were highly successful in preventing the stress response, thereby stopping the damage from obesity being passed onto the offspring.

"It restored egg quality, embryo development and mitochondrial DNA to levels equivalent to those of a healthy mother. Effectively, the problem was fully reversed," she said.

Robker said the results of this work point towards a potential future therapy to restore "natural" fertility in obese women, and to prevent multi-generational damage passing onto their children.

The study is published in the journal Development.