Egg's energy stores key to preserving fertility

October 06, 2005

DURHAM, N.C. - 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.

The oocytes lived longer when provided with the simple sugar building blocks needed to fuel metabolism, "like fattening them up to keep them alive," Kornbluth said. Further detective work revealed the reason why: a molecular pathway involved in metabolizing the sugar is directly linked to an enzyme called caspase-2, which causes apoptosis. Caspases are enzymes that chew up and destroy cells during the apoptosis process.

When the Duke team "fed" the simple sugars to frog eggs and oocytes, they shut off apoptosis. Conversely, preventing eggs from metabolizing these sugars and using the molecular pathway quickly prompted cell death, the researchers found.

The link between an egg's energy stores and the caspase-2 enzyme is especially important because previous studies showed that turning off caspase-2 in mice prevents oocytes from dying, even in response to toxic agents like chemotherapy drugs, said Seth Margolis, Ph.D., a study co-author and postdoctoral researcher in Duke's department of pharmacology and cancer biology. Also, female mice missing the gene to produce caspase-2 are born with an excess number of oocytes.

"We've really demonstrated that caspase-2 is the thing required for oocyte death, and provided a specific molecular mechanism that can keep it shut off," Margolis said.
-end-
Collaborators on the study include Mette Jensen, Catherine Herman and Jeffrey Rathmell of Duke, and William Dunphy of the California Institute of Technology.

Duke University Medical Center

Related Cell Death Articles from Brightsurf:

Cell death in porpoises caused by environmental pollutants
Environmental pollutants threaten the health of marine mammals. This study established a novel cell-based assay using the fibroblasts of a finless porpoise stranded along the coast of the Seto Inland Sea, Japan, to better understand the cytotoxicity and the impacts of environmental pollutants on the porpoise population.

Gold nanoparticles to save neurons from cell death
An international research team coordinated by Istituto Italiano di Tecnologia in Lecce (Italy) has developed gold nanoparticles able to reduce the cell death of neurons exposed to overexcitement.

New light shone on inflammatory cell death regulator
Australian researchers have made significant advances in understanding the inflammatory cell death regulatory protein MLKL and its role in disease.

Silicones may lead to cell death
Silicone molecules from breast implants can initiate processes in human cells that lead to cell death.

New players in the programmed cell death mechanism
Skoltech researchers have identified a set of proteins that are important in the process of apoptosis, or programmed cell death.

Tumors hijack the cell death pathway to live
Cancer cells avoid an immune system attack after radiation by commandeering a cell signaling pathway that helps dying cells avoid triggering an immune response, a new study led by UTSW scientists suggests.

How trans fats assist cell death
Tohoku University researchers in Japan have uncovered a molecular link between some trans fats and a variety of disorders, including cardiovascular and neurodegenerative diseases.

Bacteria can 'outsmart' programmed cell death
To be able to multiply, bacteria that cause diarrhoea block mediators of programmed cell death, a new study in 'Nature Microbiology' shows.

Cell death or cancer growth: A question of cohesion
Activation of CD95, a receptor found on all cancer cells, triggers programmed cell death -- or does the opposite, namely stimulates cancer cell growth.

Cell death blocker prevents healthy cells from dying
Researchers have discovered a proof-of-concept drug that can prevent healthy cells from dying in the laboratory.

Read More: Cell Death News and Cell Death Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.