Moley, Kelle , MD
Obesity, oocyte quality and reproductive outcomes
General Research Subject: Obesity
Focus: Obesity, Obesity\Animal Models, Obesity\Pathogenesis, Pregnancy, Pregnancy\Role of Leptin in Fetal Growth
Type of Grant: Basic Science
Project Start Date: July 1, 2013
Project End Date: June 30, 2016
Obesity in reproductive age women has hit epidemic proportions and this metabolic condition has grave consequences for the infants that are born to these women. We have established an obesity mouse model that recapitulates the phenotype seen in pre-pregnancy morbidly obese women. In this application, we focus on the oocyte as the primary site that gives rise to reproductive defects and we attempt to identify novel mechanisms responsible for these phenomenon. We focus on the metabolism of the egg and the changes that occur in the obese mother. Our objective is to investigate the mechanisms that exist to explain the abnormal nuclear findings as well as the growth abnormalities in the offspring, in the hopes that the reproductive sequelae of maternal obesity can be reduced by novel interventions and/or therapeutics.
What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?
Obesity combined with diabetes in reproductive aged women is on the rise. These patients have increased pregnancy complications such as subfertility (a longer time to conception), miscarriages and malformed infants. Recent clinical data suggests that this is oocyte specific. Obese women undergoing IVF with donor oocyte were able to avoid these complications by a highly significant factor.
This project seeks to determine the mechanism responsible for this poor reproductive performance with obesity using a mouse model which recapitulates the human disorder. It is also our goal to determine if this event can be reversed and/or prevented.
If a person with diabetes were to ask you how your project will help them in the future,
how would you respond?
Instead of diabetes and obesity causing problems during pregnancy, our work suggests that obesity has significant affects on the germ cell or oocyte before fertilization even occurs. We believe that the ultimate take home message is that losing weight and controlling blood sugar prior to pregnancy is key, however, this project will test that assumption. It is not clear if weight loss will reverse these effects on the earliest stages of oocyte maturation.
Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your research efforts?
I have been involved in diabetes and pregnancy research my entire academic career. It is my belief that the poor reproductive outcomes of these women are modifiable and preventable. Our recent findings suggest that the damage from this disease is occur even before fertilization occurs. This is a paradigm shift in our thinking about pregnancy and diabetes/obesity. Having determined this early event, I am determined to discover if this is reversible or preventable. This may be only due to diet and exercise; alternatively if the molecular pathways responsible are discovered, therapeutic targets might be identified and used along with exercise and diet to improve pregnancy outcomes.
In what direction do you see the future of diabetes research going?
Since the prevalence of obesity and diabetes is on the rise among young women of reproductive age, it is critical to pursue this line of research. Our work also suggests that infants of obese mothers are 7-10X more likely to develop obesity in childhood. Our animal research suggests that this is due to a transgenerational effect, most likely started in the oocyte and possibly the oocyte mitochondria. Exploring the possibility that the oocyte is responsible in part for the passage of obesity and diabetes to the offspring is a new area of research for the diabetes field.
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