Oocyte generation in adult mammalian ovaries by putative germ cells in bone marrow and peripheral blood.
It has been suggested that germline stem cells maintain oogenesis in postnatal mouse ovaries. Here we show that adult mouse ovaries rapidly generate hundreds of oocytes, despite a small premeiotic germ cell pool. In considering the possibility of an extragonadal source of germ cells, we show expression of germline markers in bone marrow (BM). Further, BM transplantation restores oocyte production in wild-type mice sterilized by chemotherapy, as well as in ataxia telangiectasia-mutated gene-deficient mice, which are otherwise incapable of making oocytes. Donor-derived oocytes are also observed in female mice following peripheral blood transplantation. Although the fertilizability and developmental competency of the BM and peripheral blood-derived oocytes remain to be established, their morphology, enclosure within follicles, and expression of germ-cell- and oocyte-specific markers collectively support that these cells are bona fide oocytes. These results identify BM as a potential source of germ cells that could sustain oocyte production in adulthood.
Johnson
Joshua
J
Vincent Center for Reproductive Biology, Vincent Obstetrics and Gynecology Service, Harvard Medical School, Boston, Massachusetts 02114, USA.
Bagley
Jessamyn
J
Skaznik-Wikiel
Malgorzata
M
Lee
Ho-Joon
HJ
Adams
Gregor B
GB
Niikura
Yuichi
Y
Tschudy
Katherine S
KS
Tilly
Jacqueline Canning
JC
Cortes
Maria L
ML
Forkert
Randolf
R
Spitzer
Thomas
T
Iacomini
John
J
Scadden
David T
DT
Tilly
Jonathan L
JL
D000328:Adult; D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D015415:Biomarkers / Q000378:metabolism; D001853:Bone Marrow / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology*; D016026:Bone Marrow Transplantation; D018797:Cell Cycle Proteins / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D006801:Humans; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009865:Oocytes / Q000166:cytology*; D009866:Oogenesis; D010053:Ovary / Q000166:cytology*; D036102:Peripheral Blood Stem Cell Transplantation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D013245:Sterilization, Reproductive; D025521:Tumor Suppressor Proteins / Q000235:genetics
D015415:Biomarkers; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse; D017346:Protein Serine-Threonine Kinases