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Cell. 2005 Jul 29;122(2):303-15.
g- P* q5 ]2 b' UOocyte generation in adult mammalian ovaries by putative germ cells in bone marrow and peripheral blood.
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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.8 N" N6 M0 S$ L+ [+ W+ y& o
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Vincent Center for Reproductive Biology, Vincent Obstetrics and Gynecology Service, Harvard Medical School, Boston, Massachusetts 02114, USA.
) z" m @' j2 GAbstract
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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.
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( Y8 r y% `: y3 q: f9 IPMID: 16051153 [PubMed - indexed for MEDLINE]
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' S" @# Y* j) f' E7 PPublication Types, MeSH Terms, Substances, Grant Support
- e$ e# i2 y# KPublication Types:+ { T. Z4 P! f( L2 T, T
* W8 {' l, a) U * Research Support, N.I.H., Extramural
( I: m$ ~+ a8 _1 [% T- T, Q# Q# I' r * Research Support, Non-U.S. Gov't
8 n' y5 B& H! ]7 V0 K3 M( Y+ S * Research Support, U.S. Gov't, P.H.S.5 t, K; p1 ^6 C: ^1 y% l& s3 e
# l# I8 g3 c3 Q! a( CMeSH Terms:
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. q$ D+ J2 z U, i * Adult
; m( p, x" m# |) B v. Y: P/ u * Animals) z' ?* W B& c3 k# u
* Biological Markers/metabolism; Y( K* j% N5 U7 v+ t0 @ E$ o. m
* Bone Marrow/metabolism |; `6 {- |+ U$ I; Y: L# C
* Bone Marrow Cells/cytology*
2 u# H& x9 ^) d3 [+ X * Bone Marrow Transplantation( a# g1 U) v' n& J3 Y
* Cell Cycle Proteins/genetics. p$ H c/ W2 A2 \
* DNA-Binding Proteins/genetics" M8 @& |. F" G
* Female/ [/ ]4 B4 Z1 e
* Humans
1 I7 x5 P: d: h0 ~9 \0 d * Mice7 r- y- f, q, L% F
* Mice, Mutant Strains
/ z( L) j* K3 X: g0 S, Q3 A/ ` * Mice, Transgenic' v5 B+ D4 E2 Z0 a
* Oocytes/cytology*
9 w! N/ U H* n * Oogenesis& }+ a+ Q# X2 \8 \: Y& i6 |
* Ovary/cytology*6 L8 j4 h/ {3 ^) y6 z
* Peripheral Blood Stem Cell Transplantation# m3 j2 z$ e6 D: h
* Protein-Serine-Threonine Kinases/genetics. ]4 n/ p" S: h
* Sterilization, Reproductive3 Z, r5 \% K4 q D4 t
* Tumor Suppressor Proteins/genetics
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Substances:/ G: J" v2 b$ ?! {: j0 q* V/ w
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* Biological Markers [9 M' a3 R" S2 k% C
* Cell Cycle Proteins
9 n m, C' v# u * DNA-Binding Proteins
2 X2 z2 W J* w3 e0 C/ J * Tumor Suppressor Proteins
" F! S! M1 Y2 n * ataxia telangiectasia mutated protein
3 k, O3 N% h, q4 x6 u# M * Protein-Serine-Threonine Kinases5 h" ?7 P& _! X$ ~( H+ Y; P" Q. |
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Grant Support:
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* R01-AG012279/AG/NIA NIH HHS/United States; d) U7 @4 l: M, T" l
* R01-AG024999/AG/NIA NIH HHS/United States, X& x4 y5 R5 a* T6 z6 P2 M7 W
* R01-ES08430/ES/NIEHS NIH HHS/United States
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