• Carolyn is a staff writer for Science and is the editor of the News of the Week section.

Eggs Won't Run on Empty

6 October 2005 (All day)

Low on fuel. When nutrient supplies run low, egg cells die.

Until technology takes some giant leaps, women are stuck with the egg supply they're born with. But scientists have now found that fattening up the eggs with plenty of nutrients may help them live longer. The study found a direct link between inadequate food supply to egg cells and cell death, opening up a promising new avenue for infertility research.

Every female vertebrate has a finite supply of eggs. Once a woman sails past her mid-thirties, her eggs increasingly succumb to apoptosis, or internally triggered cell death. Certain diseases and chemotherapy can also wipe out the egg supply. In 1998, scientists linked cell death to an "executioner" enzyme called caspase-2. Mice lacking caspase-2 not only had extra egg cells, but also chemotherapy-resistant ones to boot.

Now, a lingering question is what signals the executioner to strike. Cell biologist Sally Kornbluth of Duke University Medical Center in Durham, North Carolina, thought the enzyme might be regulated by how much nutrient an egg receives from its own internal stores. To check this, Kornbluth and her team altered the supply of glucose-6-phosphate, or G6P, a molecule formed during the conversion of glucose to energy, to extracts from frogs' eggs. When the glucose was high, they found, it kept a food-to-energy metabolic pathway humming, and that kept the executioner enzyme at bay. Cut off the glucose supply, though, and the enzyme went back to its grim work.

Kornbluth explains her results like this: When a cell churns glucose into energy, one byproduct of metabolism is a molecule called NADPH. When the cell's store of NADPH is above a certain threshold, the molecule continuously activates an enzyme called CaM kinase-2, which in turn keeps caspase-2 switched off. That protects the eggs, the scientists report in the 6 October Cell.

These early findings won't quickly translate to infertility treatments, Kornbluth warns. First, she wants to determine exactly how NADPH promotes the executioner-suppressing enzyme. "We haven't even begun to touch on hormonal influences" or the effects of aging on both nutrient supply and the activity of enzymes that use the nutrients, she adds.

It's an important study, says cell biologist Junying Yuan of Harvard Medical School in Cambridge, Massachusetts, who was a co-author on the earlier experiments that identified the importance of caspase-2. "We couldn't figure out how it worked," she adds. "It's a nice explanation to a long-standing puzzle."

Related sites
Sally Kornbluth's site
Junying Yuan's site
Fertility Information from NIH

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