title: Oocyte generation in adult mammalian ovaries by putative germ cells in bone marrow and peripheral blood.
abstract: 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.
authors.affiliation: Vincent Center for Reproductive Biology, Vincent Obstetrics and Gynecology Service, Harvard Medical School, Boston, Massachusetts 02114, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Johnson
authors.forename: Jessamyn
authors.initials: J
authors.lastname: Bagley
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Skaznik-Wikiel
authors.forename: Ho-Joon
authors.initials: HJ
authors.lastname: Lee
authors.forename: Gregor B
authors.initials: GB
authors.lastname: Adams
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Niikura
authors.forename: Katherine S
authors.initials: KS
authors.lastname: Tschudy
authors.forename: Jacqueline Canning
authors.initials: JC
authors.lastname: Tilly
authors.forename: Maria L
authors.initials: ML
authors.lastname: Cortes
authors.forename: Randolf
authors.initials: R
authors.lastname: Forkert
authors.forename: Thomas
authors.initials: T
authors.lastname: Spitzer
authors.forename: John
authors.initials: J
authors.lastname: Iacomini
authors.forename: David T
authors.initials: DT
authors.lastname: Scadden
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Tilly
mesh_terms: 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
chemical_list: 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