This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Anderson, R. A. Articles by Spears, N. Search for Related Content PubMed PubMed Citation Articles by Anderson, R. A. Articles by Spears, N.

Neurotropins and Their Receptors Are Expressed in the Human Fetal Ovary

Medical Research Council Human Reproductive Sciences Unit, Center for Reproductive Biology, and Section of Biomedical Sciences (N.S.), University of Edinburgh, Edinburgh, United Kingdom EH3 9ET

Address all correspondence and requests for reprints to: Dr. R. A. Anderson, Medical Research Council Human Reproductive Sciences Unit, Center for Reproductive Biology, 37 Chalmers Street, Edinburgh, United Kingdom EH3 9ET. E-mail: r.a.anderson{at}hrsu.mrc.ac.uk

Abstract

Mammalian ovarian development is characterized by a sequential pattern of mitotic proliferation of oogonia, initiation then arrest of meiosis, and primordial follicle formation. The factors regulating these processes are poorly understood. The neurotropins are survival and differentiation factors in the nervous system, acting via high affinity receptors of the trk protooncogene family and the low affinity p75 nerve growth factor receptor, and have also been described in the rodent ovary, where changes in NT4/TrkB gene expression have been detected at the time of primordial follicle formation. There are no data on neurotropin expression in the normal human ovary. We have investigated the expression and localization of neurotropins and their receptors in the midtrimester human fetal ovary (13–21 wk gestation). Expression of mRNA for neurotropins and their receptors was detected by RT-PCR. Clusters of oogonia were found to be the predominant site of NT4 mRNA expression using in situ hybridization. However, at later gestations granulosa cells of primordial follicles showed increased expression, with lesser expression in the enclosed oocytes. NT4 protein was also localized to the granulosa cells by immunohistochemistry and at earlier developmental stages to epithelioid cells, which were mingled with clusters of oogonia not expressing NT4. TrkB receptor protein was localized by immunohistochemistry to germ cells at all gestations examined. The p75 nerve growth factor receptor protein was exclusively expressed in the ovarian stroma. These data demonstrate the expression of neurotropins and their receptors within the human fetal ovary. Developmental changes in the pattern of expression of NT4 around the time of primordial follicle formation suggest that neurotropins may be involved in signaling between somatic cells and germ cells at this crucial stage of ovarian development.

This article has been cited by other articles:

				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]

				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]

				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]

				N. A. Wahab, B. S. Weston, and R. M. Mason Connective Tissue Growth Factor CCN2 Interacts with and Activates the Tyrosine Kinase Receptor TrkA J. Am. Soc. Nephrol., February 1, 2005; 16(2): 340 - 351. [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]

				N. Spears, M. D. Molinek, L. L. L. Robinson, N. Fulton, H. Cameron, K. Shimoda, E. E. Telfer, R. A. Anderson, and D. J. Price The role of neurotrophin receptors in female germ-cell survival in mouse and human Development, November 15, 2003; 130(22): 5481 - 5491. [Abstract] [Full Text] [PDF]

				L. L. L. Robinson, J. Townsend, and R. A. Anderson The Human Fetal Testis Is a Site of Expression of Neurotrophins and Their Receptors: Regulation of the Germ Cell and Peritubular Cell Population J. Clin. Endocrinol. Metab., August 1, 2003; 88(8): 3943 - 3951. [Abstract] [Full Text] [PDF]

				D. B. Seifer, B. Feng, R. M. Shelden, S. Chen, and C. F. Dreyfus Neurotrophin-4/5 and Neurotrophin-3 Are Present within the Human Ovarian Follicle but Appear to Have Different Paracrine/Autocrine Functions J. Clin. Endocrinol. Metab., October 1, 2002; 87(10): 4569 - 4571. [Abstract] [Full Text] [PDF]

				P. S. Hartley, R. A. L. Bayne, L. L. L. Robinson, N. Fulton, and R. A. Anderson Developmental Changes in Expression of Myeloid Cell Leukemia-1 in Human Germ Cells during Oogenesis and Early Folliculogenesis J. Clin. Endocrinol. Metab., July 1, 2002; 87(7): 3417 - 3427. [Abstract] [Full Text] [PDF]