Published online 5 June 2001 | Nature | doi:10.1038/news010607-5

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The majority of women's potential eggs face a fatal outcome.

Self-destructive eggs fragment into many small bodies. © J. Tilly

A baby girl comes into the world having already discarded far more eggs than she could ever use. The causes of this attrition are many and varied, say US researchers. Their studies on the death of egg cells in mice may eventually help women with abnormally scant supplies1.

A 20-week-old female fetus has around 7 million potential egg cells, or oocytes, in her developing ovaries. By birth this number has dropped to 1 million, and by puberty it is a mere 300,000. Programmed cell death - apoptosis - takes the oocytes out.

'Death by neglect' is one possible explanation for the cells' mysterious demise: excess oocytes wither away when they fail to make contact with support cells lining the ovary. 'Death by defect' is another possibility: cells that stall during division are wiped out.

But Jonathan Tilly of Massachussetts General Hospital in Boston says that "there is little hardcore evidence for either [hypothesis]".

In fact, Tilly's team found that both occur in the prenatal ovaries of mice. The researchers studied mice that lacked genes required either for the production of the growth factors that sustain oocytes or for cell division. And they found that distinct killer molecules are involved in each form of apoptosis. "They recruit different executioners to get to the same end-point," says Tilly.

Oocytes that stalled during cell division could not be saved from death even with genetic tweaking, the group went on to show. Tilly suspects that the body puts in a quality control check to screen out bad eggs which cannot be overridden. This ensures that genetic faults arising from incorrect cell division are not passed on.

Self-destructive eggs fragment into many small bodies. © J. Tilly

At puberty, around 15 oocytes start to mature in each menstrual cycle. One of these is chosen for release and the rest die off.

The most healthy egg - "the one that gets ahead of the pack" - may out-compete the rest, explains Zev Rosenwaks, a reproductive and infertility specialist at Cornell University in Ithaca, New York.

If a woman's supply of oocytes runs out she will enter the menopause. For some, this occurs at an abnormally young age because their stock runs out early. Cancer treatments can also cut the numbers of potential eggs, leading to infertility.

Understanding the natural mechanisms that kill off oocytes may help scientists to develop therapies to rescue competent eggs in these conditions. "But it's more a theory than a reality," cautions Rosenwaks.