An immature egg's internal nutrient supply is critical to its survival, an insight that offers a new route to understanding and treating infertility due to egg death, according to Duke University Medical Center researchers.
As women age, their stockpile of immature eggs, called oocytes, diminishes through cell death, eventually leading to infertility. In studies with frog oocytes, the Duke researchers found that the nutrient storehouse, or yolk, plays a key role in regulating the survival of these cells. Depleting the nutrients triggers apoptosis – programmed cell death – and adding nutrients prolongs the life of eggs, they found. The study offers potential for developing oocyte-protective therapies for women undergoing chemotherapy, as well as potential targets for improved infertility treatments, the researchers said.
"This discovery provides a basic science underpinning for understanding the mechanisms of oocyte death and a way to identify potential clinical treatments," said Sally Kornbluth, Ph.D., senior study author and an associate professor of pharmacology and cancer biology at Duke University Medical Center.
Adds Leta Nutt, Ph.D., lead author of the study, "Our work provides evidence for a metabolic timer in which oocytes that use up their energy stores are fated to die." Nutt is a postdoctoral researcher in Duke's department of pharmacology and cancer biology.
The results appear in the Oct. 7, 2005, issue of Cell. The work was supported by the National Institutes of Health, the Sidney Kimmel Foundation for Cancer Research, the V Foundation for Cancer Research and the Triangle Community Foundation.
Oocytes are one of the few cells to rely entirely on internal energy stores, receiving no nutrients from the body. Human oocytes have a relatively small nutrient stockpile compared to the frog oocytes studied by the Duke researchers.
To explore the link between energy stores and apoptosis (cell death), the researchers both extended the lifetime of frog oocytes by feeding them nutrients and triggered apoptosis by mimicking a lack of nutrients.