Improving Pregnancy Outcomes in Obese Mothers Starts with Healthy Eggs
More than a third of women of childbearing age are now estimated to be obese. Obese women have increased rates of infertility, and once they are pregnant, they experience higher rates of miscarriage, gestational diabetes, preeclampsia, and other pregnancy complications. Further, the children of overweight and obese mothers have an increased risk of developmental delays and other neurological deficits, and are more likely to develop obesity, diabetes and related complications themselves as they become adults. It is critical to understand how obesity impacts reproduction, not only for women seeking to become pregnant now, but also for the health and wellness of future generations.
Maternal obesity can affect various steps in the reproductive process, but clinical data suggest that the quality of a woman's oocyte, or egg, may be particularly important. Eggs from obese women have a higher prevalence of structural abnormalities that disrupt chromosome alignment during cell division. These defects diminish the egg's ability to be fertilized and for the embryo to develop normally following fertilization. Interestingly, a recent study showed that while in vitro fertilization (IVF) success is reduced in obese women using their own eggs, when eggs from lean donors were used, pregnancy success was improved. These observations imply that the quality of the egg, independent of the mother's metabolic status, may contribute significantly to fertility and pregnancy outcomes.
American Diabetes Association-funded researcher Dr. Kelle Moley is working to better understand how overweight and obesity may impact oocyte quality. In preliminary work using a mouse model of diet-induced obesity, Dr. Moley showed that a high fat diet resulted in significant structural defects in oocytes, including the structures that correctly arrange chromosomes into the dividing cells. As a result, a higher prevalence of oocytes in the obese animals had misaligned chromosomes. These defects led to reduced fertility and increased fetal defects in the mice. All of these changes in the oocyte were similar to those observed in human eggs.
She found that moving obese animals from a high fat diet to a healthier diet normalized metabolic parameters such as weight, blood sugar and lipid levels. However, the change in diet did not reverse oocyte defects, and the chromosome alignment abnormalities remained. In a second set of experiments, she tested whether exercise could reverse oocyte defects resulting from high fat diet. The addition of exercise did improve some markers of oocyte health, but still did not resolve the chromosome defects. Therefore, despite improved metabolic health in the mother, the oocyte defects induced by high fat diet were not easily reversible by diet or exercise, suggesting that weight loss prior to conception may not be sufficient to correct oocyte health. I If replicated in humans, the results could directly guide pre-conception recommendations for obese women regarding the potential effects that weight loss will have on their chances of becoming pregnant.
Dr. Moley's future aims are to figure out exactly how high fat diet and obesity affect egg quality. Understanding exactly how obesity leads to changes in oocyte health will provide avenues for therapeutic approaches to improve pregnancy outcomes and the health of children born to obese women.