University of Adelaide - An Australian researcher has discovered scientific evidence that obesity associated with a high-fat diet is a key factor in infertility – because of how it affects the receptor PPARγ in women’s eggs. PPAR-gamma has an insulin-sensitizing effect in the body; it is one of the PPAR set of receptors associated with fat metabolism.

It is not only being underweight from excessive dieting or anorexia nervosa that causes infertility. Obesity has long been thought to be a major factor in couples’ inability to conceive, but this is the first time the effects of obesity on the egg have been discovered.

The research findings – using female mice – have been made by PhD student Cadence Minge in the University of Adelaide’s Research Centre for Reproductive Health.

Importantly, her research has also discovered a way to completely reverse the effects of obesity on mouse eggs, enabling afflicted eggs to develop into healthy embryos.

“Consuming a diet high in fat causes damage to eggs stored in female ovaries. As a result, when fertilized, these eggs are not able to undergo normal, healthy development into embryos,” Ms Minge says.

Ms Minge has discovered that a protein in the cells surrounding, supporting and nourishing the egg – called Peroxisome Proliferator-Activated Receptor gamma (PPARγ) – is the main reason behind diet-induced infertility.

“The behavior of this protein helps to determine the way in which the ovaries sense and respond to fats,” Ms Minge says.

“Being able to control this protein will be very important in the quest to reverse infertility caused by poor diets.”

Ms Minge’s research has found that when the protein is selectively targeted with the anti-diabetes drug rosiglitazone (marketed as Avandia(R) by GlaxoSmithKline), the adverse effects of obesity on egg quality are completely reversed.

“The drug enables us to switch on the protein, thereby changing the way in which the ovaries sense and respond to fats. Embryo development rates are restored, and the cellular differentiation of the early embryo is improved. In the long-term these improvements can result in increased birth weight and fetal survival,” Ms Minge says.

However, Ms Minge warns that rosiglitazone should not be seen as a “quick fix” for overweight infertile women.

“The rosiglitazone findings are of great significance for scientists researching egg maturation within the ovary. But at this stage, the research findings have only been made in mice. Also, the drug itself can have possible harmful side-effects, and more research is needed to find other, safer ways of activating the protein,” she says.

“With more research, if we can pinpoint critical cellular controls of egg quality, it may allow women to maximise their likelihood of healthy conception.”

Ms Minge says her findings emphasize the importance of a healthy lifestyle for women interested in conceiving children naturally. [Essential fatty acids like the omega-3 DHA are known to affect some PPAR receptors, like PPAR-alpha, but it is not clear which if any EFAs affect PPAR-gamma, especially in normal dietary intake ranges.]

“I hope that these findings encourage people to carefully consider the impact of lifestyle choices on longer-term quality of life.”

“Despite the wide-ranging recognized health risks associated with excessive body weight, Australia’s waistline continues to expand. Currently, Australia is on par with heavyweight nations such as the US and the UK, with approximately 60% of Australian adults now overweight or obese,” Ms Minge says.