|
|
|
|
|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | ||||
First published online 24 September 2003
doi: 10.1242/dev.00707
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Biomedical Sciences, University of Edinburgh, Hugh Robson Building, George
Square, Edinburgh EH8 9XD, UK
2 Medical Research Council Human Reproductive Sciences Unit, Centre for
Reproductive Biology, The University of Edinburgh Chancellor's Building, 49
Little France Crescent, Edinburgh EH16 4SA, UK
3 Institute of Cellular and Molecular Biology, University of Edinburgh, Darwin
Building, Kings Buildings, Edinburgh, UK
* Author for correspondence (e-mail: norah.spears{at}ed.ac.uk)
Accepted 4 July 2003
During mammalian ovary formation, the production of ovarian follicles is accompanied by an enormous loss of germ cells. It is not known how this loss is regulated. We have investigated the role of the Trk tyrosine kinase receptors, primarily TrkB, in this process. The ovaries of TrkB–/– and TrkC–/– mice with a mixed (129Sv x C57BL/6) genetic background were examined shortly after birth. Around 50% of TrkB–/– mice had grossly abnormal ovaries that contained greatly reduced numbers of follicles. No defects were found in the ovaries of TrkC–/– mice. Congenic TrkB–/– mice were generated on 129Sv and C57BL/6 backgrounds: whereas the former had a mixed ovarian phenotype similar to that of the original colony of mice, the ovaries of all offspring of the C57BL/6 congenic line contained reduced numbers of follicles. RT-PCR showed that mRNA encoding TrkB and its two ligands, neurotrophin 4 (NT4) and brain-derived neurotrophic factor (BDNF), were present throughout the period of follicle formation in the mouse. In situ hybridisation showed that TrkB was expressed primarily in the germ cells before and after follicle formation. Mouse neonatal and fetal ovaries and human fetal ovaries were cultured in the presence of K252a, a potent inhibitor of all Trk receptors. In mice, K252a inhibited the survival of germ cells in newly formed (primordial) follicles. This effect was rescued by the addition of basic fibroblast growth factor (bFGF) to the culture medium. Combined addition of both BDNF and NT4 blocking antibodies lowered germ-cell survival, indicating that these TrkB ligands are required in this process. The results indicate that signalling through TrkB is an important component of the mechanism that regulates the early survival of female germ cells.
Key words: Trk, Oogonia, Oocyte, Survival, Human, Mouse, Neurotrophin
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
 |
|
  B. Kerr, C. Garcia-Rudaz, M. Dorfman, A. Paredes, and S. R Ojeda NTRK1 and NTRK2 receptors facilitate follicle assembly and early follicular development in the mouse ovary Reproduction, July 1, 2009; 138(1): 131 - 140. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. A McLaughlin and S. C McIver Awakening the oocyte: controlling primordial follicle development Reproduction, January 1, 2009; 137(1): 1 - 11. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. De La Chesnaye, B. Kerr, A. Paredes, H. Merchant-Larios, J. P. Mendez, and S. R. Ojeda Fbxw15/Fbxo12J Is an F-Box Protein-Encoding Gene Selectively Expressed in Oocytes of the Mouse Ovary Biol Reprod, April 1, 2008; 78(4): 714 - 725. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Lee, Y. I. Jeong, S. M. Park, J. Y. Lee, J. H. Kim, S. W. Park, M S Hossein, Y. W. Jeong, S. Kim, S. H. Hyun, et al. Beneficial effects of brain-derived neurotropic factor on in vitro maturation of porcine oocytes Reproduction, September 1, 2007; 134(3): 405 - 414. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Rajareddy, P. Reddy, C. Du, L. Liu, K. Jagarlamudi, W. Tang, Y. Shen, C. Berthet, S. L. Peng, P. Kaldis, et al. p27kip1 (Cyclin-Dependent Kinase Inhibitor 1B) Controls Ovarian Development by Suppressing Follicle Endowment and Activation and Promoting Follicle Atresia in Mice Mol. Endocrinol., September 1, 2007; 21(9): 2189 - 2202. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Garcia-Rudaz, F. Luna, V. Tapia, B. Kerr, L. Colgin, F. Galimi, G. A. Dissen, N. D. Rawlings, and S. R. Ojeda Fxna, a novel gene differentially expressed in the rat ovary at the time of folliculogenesis, is required for normal ovarian histogenesis Development, March 1, 2007; 134(5): 945 - 957. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K.R. Barnett, C. Schilling, C.R. Greenfeld, D. Tomic, and J.A. Flaws Ovarian follicle development and transgenic mouse models Hum. Reprod. Update, September 1, 2006; 12(5): 537 - 555. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Salas, M. Julio-Pieper, M. Valladares, R. Pommer, M. Vega, C. Mastronardi, B. Kerr, S. R. Ojeda, H. E. Lara, and C. Romero Nerve Growth Factor-Dependent Activation of trkA Receptors in the Human Ovary Results in Synthesis of Follicle-Stimulating Hormone Receptors and Estrogen Secretion J. Clin. Endocrinol. Metab., June 1, 2006; 91(6): 2396 - 2403. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Harel, S. Jin, B. Fisch, D. Feldberg, H. Krissi, C. Felz, S. Freimann, S.L. Tan, A. Ao, and R. Abir Tyrosine kinase B receptor and its activated neurotrophins in ovaries from human fetuses and adults Mol. Hum. Reprod., June 1, 2006; 12(6): 357 - 365. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Fulton, S. J. Martins da Silva, R. A. L. Bayne, and R. A. Anderson Germ Cell Proliferation and Apoptosis in the Developing Human Ovary J. Clin. Endocrinol. Metab., August 1, 2005; 90(8): 4664 - 4670. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Kawamura, N. Kawamura, S. M. Mulders, M. D. Sollewijn Gelpke, and A. J. W. Hsueh Ovarian brain-derived neurotrophic factor (BDNF) promotes the development of oocytes into preimplantation embryos PNAS, June 28, 2005; 102(26): 9206 - 9211. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Abir, B. Fisch, S. Jin, M. Barnnet, A. Ben-Haroush, C. Felz, G. Kessler-Icekson, D. Feldberg, S. Nitke, and A. Ao Presence of NGF and its receptors in ovaries from human fetuses and adults Mol. Hum. Reprod., April 1, 2005; 11(4): 229 - 236. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S J Martins da Silva, J O Gardner, J E Taylor, A Springbett, P A De Sousa, and R A Anderson Brain-derived neurotrophic factor promotes bovine oocyte cytoplasmic competence for embryo development Reproduction, April 1, 2005; 129(4): 423 - 434. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Uda, C. Ottolenghi, L. Crisponi, J. E. Garcia, M. Deiana, W. Kimber, A. Forabosco, A. Cao, D. Schlessinger, and G. Pilia Foxl2 disruption causes mouse ovarian failure by pervasive blockage of follicle development Hum. Mol. Genet., June 1, 2004; 13(11): 1171 - 1181. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A.L. Bayne, S. J. Martins da Silva, and R. A. Anderson Increased expression of the FIGLA transcription factor is associated with primordial follicle formation in the human fetal ovary Mol. Hum. Reprod., June 1, 2004; 10(6): 373 - 381. [Abstract] [Full Text] [PDF]
|
|
