Adelaide University. Australia: In a breakthrough discovery, researchers at the University of Adelaide
have revealed how damage from obesity is passed from a mother to her
children, and also how that damage can be reversed.
The findings, by a team led by the University's Robinson Research Institute, have major implications for the future of fertility research and are published today in the journal Development.
"It's
now well established that obesity in females leads to very serious
fertility problems, including the inability to conceive. Obesity can
also result in altered growth of babies during pregnancy, and it
permanently programs the metabolism of offspring, passing the damage
caused by obesity from one generation to the next," says lead author Associate Professor Rebecca Robker from the Robinson Research Institute.
"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," Associate Professor Robker says.
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 says.
Having pinpointed the problem, Associate Professor Robker and her colleagues 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," Associate Professor Robker says.
"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."
Associate Professor Robker says 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.
"Importantly, this work further
highlights that a woman'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," she says.
This research is supported by the National Health and Medical Research Council (NHMRC).