Obese women can improve their odds of conceiving with the help of pharmaceuticals, a new study from the University of Adelaide (UA) suggests.
The researchers have identified two drugs that have successfully reversed the effects of obesity on fertility in mice, renewing hope that a similar solution for “natural” fertility may be found for humans.
Obese women who are pregnant are significantly more likely to encounter pregnancy complications, including miscarriages, than lean pregnant women.
The exact mechanisms of how obesity reduces fertility in women are not fully understood but it has been linked to hormonal imbalances, abnormal changes in women’s ovulation cycles and a greater frequency of complications during pregnancy.
Even with a successful pregnancy, the children of obese women remain at risk, as they are more likely to be obese.
Considering fat mice’s fertility
Marlon Cerf, a specialist scientist with the South African Medical Research Council, said the findings of the study are “promising”, given that the country has one of the highest obesity rates in the world.
Within the nation, seven in 10 women are obese or overweight, according to a study published last year by the medical journal Lancet. Among the many health risks these women face are reduced fertility and higher odds of having children who will become obese.
“With the high prevalence of obesity in South African women, birth rates may drop and obesity may be transmitted to future generations,” Cerf says. “The transmission of obesity to subsequent generations exacerbates this vicious cycle.”
In the study, published this month in the journal Development, researchers at UA compared the unfertilised and fertilised eggs of obese mice and lean mice and found that obesity caused stress on two major cellular structures: the endoplasmic reticulum (ER), a membrane inside cells that packages and transports proteins, and mitochondria, “organs” present in every cell of the human body that are crucial to transforming sugars into usable energy.
Stress inhibitor drugs
Mitochondrial activity is especially pertinent during reproduction because, although humans inherit their DNA from both mother and father, they inherit mitochondrial DNA exclusively from the mother. In obese mice, the researchers saw that their eggs had less mitochondrial activity and transmitted less mitochondria DNA to new cells during early reproduction.
“If the mother is obese, this produces stresses that lead to reduced transmission of mitochondria to the offspring,” said Rebecca Robker, the lead author of the study. “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.”
After identifying the stress responses, the researchers looked for ways to alleviate these stresses to restore normal development. They found the solution in two stress inhibitor drugs: BGP-15, a drug undergoing human clinical trials to treat diabetes, and Salubrinal.
“These compounds were highly successful in preventing the stress response, thereby stopping the damage from obesity being passed on to the offspring,” Robker said. “It restored egg quality, embryo development and mitochondrial DNA to levels equivalent to those of a healthy mother. Effectively, the problem was fully reversed.”
Cerf said the study highlights the importance of the preconception period as a critical time for treating ER stress to improve offspring outcomes and possibly prevent obesity. But he added that “further evidence in a clinical setting is required to reinforce these promising findings”.