My question: how did this 'doctrine' get established in the first place? Did no one test this? Aren't scientists supposed to conduct experiments to test hypotheses? The article quotes skeptical scientists saying 'not so fast,' and then continues:Dr. Jonathan Tilly and his colleagues at Harvard Medical School and the Massachusetts General Hospital report in the journal Nature today that they have discovered numerous signposts of so-called germ-line stem cells in the ovaries of young and adult female mice — powerful and multitalented cells capable of generating a fresh batch of immature egg "seeds," as well as the ovarian infrastructure needed to bring these oocytes to fruition.
Moreover, the stem cells appear to be quite active, indicating that they are not a pool of insignificant holdovers from fetal development, but rather are busy creating new little egglets and their follicle housing on the surface of the adult ovary. Follicles are fluid-filled capsules in which oocytes (pronounced OH-oh-sites) ripen into fully formed eggs, capable of being fertilized.
If confirmed by other researchers, the results would upend a doctrine shared by reproductive biologists for 80 years: that a female mammal is born with all the oocytes and follicles she will ever have, and that her stock of eggs is steadily depleted until the procreation pantry is bare.
Scientists had long assumed there was no new egg growth after birth because many earlier analyses of animal and human ovarian tissue had failed to find evidence of cell growth or follicle regeneration.
Yet Dr. Tilly believes that the technology has markedly improved in recent years, and that numerous lines of evidence from four distinct experimental approaches in his laboratory all pointed toward egg regeneration. The researchers are known for their studies of programmed cell death — the process known to eliminate unwanted cells from the body, including old eggs and follicles — and they were seeking better ways to regulate cell death during chemotherapy and thus help protect fertility in cancer patients.
As they examined cell death in normal mouse ovaries, however, they began to realize that oocytes and follicles were dying so fast that a female mouse should exhaust virtually her entire natal complement of eggs by young adulthood. Yet the mice would remain fertile for 10 more months.
The scientists then wondered if all the supposed cell death they were seeing was merely an accumulation of old egg corpses. That made little sense: The body is compulsive about quick disposal of dead tissue. "Why should the ovary, of all places, be a garbage heap?" Dr. Tilly said.
Pressing forward, the researchers showed that cells were dividing on the surface of the ovary, indicating the possible replenishment of reproductive tissues. But were those replicating cells making new eggs?
The hallmark of egg creation is meiosis, the process that yields a reproductive cell with only half the number of chromosomes that occur in the rest of the body's cells. That genomically reduced egg is then equipped to merge with a similarly reduced sperm. Examining tissue from adult mouse ovaries, the researchers found signs of genetic activity unique to meiosis.
The researchers also worked with genetically engineered mice bearing jellyfish marker genes that turned their tissues fluorescent green. Grafting ovarian slices from normal mice onto the ovaries of the leprechaun mice, the researchers discovered pockets of white follicular tissue with green eggs inside, indicating that regeneration of the egg-follicle package must be occurring.
Finally, experiments with a chemotherapy drug called busulfan, known to selectively kill off sperm stem cells in men, likewise appeared to obliterate egg replacement in mice without killing existing eggs, leading to severe depletion of their egg stock over time. That busulfan is also known to cause sterility in women more thoroughly than most chemotherapy agents leads Dr. Tilly to suspect that women, too, possess germ-line stem cells vital to their fertility.
Dr. Tilly emphasizes that the most important proof of his premise remains to be captured: isolation of the stem cells proper. "You'd better believe we're working on it arduously night and day," he said.
UPDATE
Here are the citation details:A basic doctrine of reproductive biology is that most mammalian females lose the capacity for germ-cell renewal during fetal life, such that a fixed reserve of germ cells (oocytes) enclosed within follicles is endowed at birth. Here we show that juvenile and adult mouse ovaries possess mitotically active germ cells that, based on rates of oocyte degeneration (atresia) and clearance, are needed to continuously replenish the follicle pool. Consistent with this, treatment of prepubertal female mice with the mitotic germ-cell toxicant busulphan eliminates the primordial follicle reserve by early adulthood without inducing atresia. Furthermore, we demonstrate cells expressing the meiotic entry marker synaptonemal complex protein 3 in juvenile and adult mouse ovaries. Wild-type ovaries grafted into transgenic female mice with ubiquitous expression of green fluorescent protein (GFP) become infiltrated with GFP-positive germ cells that form follicles. Collectively, these data establish the existence of proliferative germ cells that sustain oocyte and follicle production in the postnatal mammalian ovary.
