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Sonia Krestchmar/COSMOS Credit: Sonia Krestchmar/COSMOS Tick, tick, tick. It's a sound only a woman can hear: the ticking of her biological clock. And it isn't metaphorical: females are born with about a million eggs and - like the sands though the hour glass - this reservoir steadily runs down. Some eggs are lost through natural ovulation. But the vast majority disintegrate, a process that snowballs once she reaches the age of 30. By the time she reaches 40 to 50, all her eggs will have gone. And with them, her chance of ever giving birth to her own baby. But U.S. researchers at Boston's Harvard University may have found a way of stopping the countdown on that seemingly omnipotent clock. Their report in the July 2005 issue of the international journal, Cell, suggests that a woman's eggs could be restocked from cells that reside in her bone marrow. It's an idea that has many researchers scratching their heads in frank disbelief. "Many of my colleagues say this is just nonsense," said Orly Lacham Kaplan, a researcher at Monash Immunology and Stem Cells Laboratories in Melbourne. "I'm more open minded: we already know bone marrow cells can do weird things like make liver or heart cells, so why not eggs?" Even Jonathan Tilly, the Harvard University scientist behind this research, wasn't expecting the result. For the past 50 years, biology textbooks have taught that, unlike men's sperm, women's eggs can never be replenished. But in 2004 Tilly's group surprised everyone with a paper in the British journal, Nature, reporting that female mice were making new eggs. They figured this out by counting how many follicles (the pods that contain an egg) in a mouse ovary were disintegrating at any one time - something no one had bothered to do before. It turned out to be a whopping one third of them. It didn't take rocket science to figure out what that meant: the mice should run out of eggs in a few weeks. But they didn't; they stayed fertile for 12 months. So new eggs must be coming from somewhere. But where? Tilly's team suspected stem cells in the ovary were making eggs, just as there are stem cells in the testis that make sperm. That turned out to be wrong. Ovary stem cells were found but their output could not account for the sheer volume of new eggs being made. For instance, all the mouse eggs could be destroyed in one fell swoop using a toxic chemical. Yet after just 24 hours, hundreds of new eggs appeared. Wondering where these vast numbers of eggs could be coming from, Tilly's thoughts turned to bone marrow, the home of the blood-forming stem cell. When a mouse is in the earliest stages of embryonic development, the blood-forming stem cell (or haematopoietic stem cell) and the egg-forming stem cell (or primordial germ cell) are near neighbours. Maybe these cells had a lot more in common than anyone had ever thought. Certainly over the last few years, claims that blood-forming stem cells could make nearly every kind of tissue have been coming thick and fast; though these claims do remain hotly contested. To test whether it could be blood stem cells coming to the rescue, the researchers made use of genetically engineered mice whose blood cells turned green if they became eggs. They transfused blood or bone marrow from this engineered mouse into a mouse whose eggs had been destroyed by a chemical. After two months, they peered into the ovaries of the recipient mouse, and saw she had normal looking eggs again, except for one thing: they were green! They had come from the blood cells. Tests showed the eggs seemed normal, but they have yet to pass the ultimate test: whether they can be fertilised and give rise to baby mice. If they do, that will be great news for mice, but what might it mean for women? According to traditional belief, a woman reaches menopause because her store of eggs reaches its 'use-by' date, usually sometime between the ages of 40 and 50 years. But if Tilly's group is right, then the picture is much more dynamic. Eggs are continuously destroyed, but also continually replaced. So when menopause or cancer chemotherapy apparently cause a woman to run out of eggs, the problem must be that egg destruction outpaces the ability to replenish them. If that's the case, it sets a new therapeutic strategy for researchers: to find a way to speed up the process of egg replenishment. "It just opens up enormous possibilities that we couldn't fathom before," Tilly said. Elizabeth Finkel is a science writer in Melbourne, a contributing editor of COSMOS, and the author of Stem Cells: Controversy on the Frontiers of Science. |
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