Bone Marrow and Peripheral Blood are Sources of Germ Cells in Mice

Jonathan L. Tilly, Ph.D.
Massachusetts General Hospital­Harvard Medical School
R01ES008430

Background: The theory that female mammals are born with a finite number of germ cells, also known as oocytes, has been accepted as an unquestionable truth for over 50 years. Mammals were thought to lose the ability to produce new oocytes during the fetal development period. Oocytes are found in the ovaries surrounded by somatic cells in structures known as follicles and only a small fraction of follicles are actually reach ovulation producing an egg capable of being fertilized. The numbers are somewhat astounding­in humans only about 30,000 of the original pool of about one million oocytes present at birth are still present at puberty. This number gradually declines throughout adulthood resulting in the complete loss of oocytes at around age 50 signaling and driving menopause. Mice have proportionately similar declines in oocyte populations resulting in the complete demise of the oocyte pool long before death due to chronological age.

Recent research has challenged this accepted dogma by showing that mice can produce oocytes and follicles during puberty and adulthood. The same occurs in flies which maintain oocyte production into adulthood due to a specialized cell population known as germline stem cells. Acceptance of the concept that adult mammals can continue to produce oocytes was been slow, likely due to the lack of direct evidence of the existence of mammalian female germline stem cells.

Advance: In new research supported in part by NIEHS, researchers at the Harvard Medical School have shown that adult mice can produce large numbers of new oocytes in a short period of time providing additional evidence to challenge the accepted belief of a fixed complement of oocytes at birth. Also, based on gene expression analysis and bone marrow transplantation studies these researchers have discovered a source of germline stem cells in the bone marrow. Other studies using peripheral blood from transgenic animals with germline cells expressing green fluorescent protein and injected into other mice that have had their bone marrow destroyed with chemotherapeutic agents show that oocytes found later in the ovary also express the fluorescent protein.

Implications: The researchers have not yet determined whether oocytes derived from germline stem cells can undergo fertilization and subsequently develop into viable offspring. However, the results do prove that bone marrow and peripheral blood are sources of the germline stem cells and can sustain oocyte production into adulthood. Much additional research is needed, but if adult oocyte production is also possible in humans, it could have major implications on the treatment of infertility and other disorders such as osteoporosis.

Citation: Johnson J, Bagley J, Skaznik-Wikiel M, Lee HJ, Adams GB, Niikura Y, Tschudy KS, Tilly JC, Cortes ML, Forkert R, Spitzer T, Iacomini J, Scadden DT, Tilly JL. Oocyte generation in adult mammalian ovaries by putative germ cells in bone marrow and peripheral blood. Cell. 2005 Jul 29;122(2):303-15.