The breakthrough discovery was made by a team at the University of Adelaide’s Robinson Research Institute led by Associate Professor Rebecca Robker.
It's now well established that female obesity can lead to serious fertility problems, including the inability to conceive. Obesity can also result in the 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.
Pinpointing the problem
"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," said Robker.
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. We found that the eggs of such mothers lead to heavier-than-normal fetuses with greatly reduced amounts of mitochondrial DNA and other obvious signs of damage," she said.
Having pinpointed the problem, Robker and her colleagues then attempted to stop it from occurring.
"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.
Damage can be reversed
"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."
Robker said the results of point towards a potential future therapy to restore "natural" fertility in obese women, and to prevent multi-generational damage passing onto their children.
"Importantly, this work further highlights that a women's nutritional state prior to getting pregnant matters greatly. Women are urged to eat healthy diets to optimise their chances for a healthy conception and to reduce the potential impact on their child's future health.”
This research is supported by the National Health and Medical Research Council (NHMRC) and published in the journal Development