Article: Mouse Study Upends Bedrock Tenet of Reproductive Biology

Discussion in 'Health and medical' started by Robert Karl Sto, Mar 17, 2004.

  1. Mouse Study Upends Bedrock Tenet of Reproductive Biology
    Alla Katsnelson

    For nearly a century, scientists have firmly believed that
    whereas men can produce sperm throughout their lives, women
    are born with all the eggs they will ever have. But new
    research suggests that this basic tenet of reproductive
    biology is wrong, a discovery that could have enormous
    repercussions for fertility treatment. Egg cells, or
    oocytes, that are not fertilized are known to undergo a
    natural process of cell death. While investigating the
    effects of chemotherapy drugs on fertility in mice, Jonathan
    L. Tilly of Massachusetts General Hospital and his
    colleagues began to count the normal rate at which oocytes
    die. "We certainly didn't set out two years ago to overturn
    dogma," says Tilly, lead author of the report detailing the
    findings, published today in Nature. But to their surprise,
    the scientists found that the number of oocytes dying over a
    period of several days was far greater than would be
    sustainable over the long term if the egg supply was not
    being replenished. In fact, at that rate, mice would be
    fertile for just two weeks following birth, as opposed to
    more than a year.

    The team subsequently conducted a series of experiments to
    verify the observation. Careful examination of the lining of
    adult mouse ovaries revealed cells that closely resemble
    germline stem cells, those continuously dividing cells that
    give birth to oocytes. The researchers determined that these
    ovarian cells express a protein that is associated with
    meiosis, the

    germline stem cells into a strain of transgenic mice whose
    cells all express a green fluorescent marker, they found
    that the transplanted cells had divided and produced oocyte
    follicles in the host tissue. Tilly and his collaborators
    also analyzed the effects of a chemotherapy agent called
    Busulfan on the mouse ovaries. The drug, which has been used
    to study sperm proliferation, destroys the ability of male
    germline stem cells to divide into new sperm, but does not
    harm existing sperm. Several weeks after injecting the
    ovaries with Busulfan, the researchers found that the number
    of oocytes had decreased dramatically. There was no sign of
    the cell death that marks oocyte degeneration, however. The
    drug apparently targeted the female stem cells, preventing
    their ability to produce oocytes.

    Early in the 20th century, some scholars had suggested that
    eggs could in fact be replenished in adult mammals. But a
    1951 study definitively argued that egg numbers are
    determined at birth, shutting the door to further work for
    the next half century. "People were viewing ovaries very
    differently than we do now," Tilly reflects. "The technology
    was just based on histological analysis." Although
    biological markers for germline stem cells have since been
    developed, conclusions about mammalian ovaries were never
    reexamined because they were believed to be "as sound as
    telling people that the sun sets in the west."

    The team is now working to demonstrate the existence of
    germline stem cells in human ovaries, and it is confident
    that the finding will carry over. The next step is to figure
    out which genes instruct a germ stem cell to differentiate
    into an egg. Ultimately, Tilly says, transplanting these
    cells into the ovaries of menopausal women or women whose
    ovaries have been prematurely damaged by cancer treatment
    could restore their fertility.

    >From Scientific American

    Posted by Robert Karl Stonjek.