Obesity comes with a variety of comorbid conditions, including diabetes, hypertension, cancer, and a number of others. One condition that doesn’t typically garner as much attention, however, is fertility issues. Obese women typically have problems conceiving, carrying the pregnancy, and their children are more likely to become obese themselves. A new paper in the journal Development from lead author Rebecca Robker from the University of Adelaide in Australia describes how a diabetes drug could improve fertility in obese females, and even lead to healthier offspring.
"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," Robker said in a press release.
In order to improve fertility and the health of the offspring, Robker’s team first had to identify the mechanism that was leading to obesity being passed down. Ultimately, they discovered that the stress of obesity was affecting mitochondria, which are responsible for generating the majority of the energy by the cells. The stress creates damage that results in decreased mitochondrial activity.
"All of the mitochondria in our bodies come from our mother,” Robker explained. “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.”
In addition to affecting mitochondria, obesity can also put stress on the endoplasmic reticulum (ER), which helps synthesize proteins and ferry them outside of the cell for dispersal around the body. Robker’s team found that egg cells from obese mice had significantly more markers for ER stress and reduced mitochondrial activity compared to egg cells from mice that were more lean. The obese mice produced offspring that were more likely to be obese and have reduced mitochondrial function than the lean mice as well.
In order to combat this stress, the researchers administered a drug currently in development for diabetes treatment. The compound effectively inhibits ER stress, promoting normal function of the cell. After obese female mice were given the drug, the propensity for obesity went away.
"These compounds were highly successful in preventing the stress response, thereby stopping the damage from obesity being passed onto the offspring,” Robker explained. “It restored egg quality, embryo development and mitochondrial DNA to levels equivalent to those of a healthy mother. Effectively, the problem was fully reversed.”
In addition to pointing at a potentially promising line of treatment for obese individuals hoping to have children, Robker also explains that this study highlights the importance of good maternal health before becoming pregnant.
[Hat tip: Kate Wheeling, Science News]