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Recombinant Growth Differentiation Factor-9 (GDF-9) Enhances Growth and Differentiation of Cultured Early Ovarian Follicles
Abstract
Transgenic mice with deletion of the GDF-9 (growth differentiation factor-9) gene are characterized by the arrest of ovarian follicle development at the primary stage. Based on the hypothesis that GDF-9 is important for early follicle development, we isolated rat GDF-9 complementary DNA (cDNA) and generated recombinant GDF-9 protein to study its physiological role. Using bacteria-derived GDF-9-glutathione S-transferase (GST) fusion protein, specific antibodies to the mature form of GDF-9 was generated. Immunohistochemical staining of ovarian sections indicated the localization of GDF-9 protein in the oocyte of primary, secondary and preantral follicles, whereas immunoblotting demonstrated the secretion of GDF-9 by mammalian cells transfected with GDF-9 cDNAs. Recombinant GDF-9 was shown to be an N-glycosylated protein capable of stimulating early follicle development. Growth of preantral follicles isolated from immature rats was enhanced by treatment with either GDF-9 or FSH whereas the combined treatment showed an additive effect. In addition, treatment with GDF-9, like forskolin, also stimulated inhibin-alpha content in explants of neonatal ovaries. In contrast, the stimulatory effects of GDF-9 were not mimicked by amino-terminal tagged GDF-9 that was apparently not bioactive. Thus, the present study demonstrates the important role of GDF-9 in early follicle growth and differentiation. The availability of recombinant bioactive GDF-9 allows future studies on the physiological role of GDF-9 in ovarian development in vivo.
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Citations
Cited by
Initial and cyclic recruitment of ovarian follicles
McGee, E. A., & Hsueh, A. J. W. (2000) · Endocrine Reviews · doi:10.1210/edrv.21.2.0394 · Cited by 1,771
Self-citationOocyte-secreted factors: regulators of cumulus cell function and oocyte quality
Gilchrist, R. B., Lane, M., & Thompson, J. G. (2008) · Human Reproduction Update · doi:10.1093/humupd/dmm040 · Cited by 1,108
Oocyte control of ovarian follicular development and function in mammals
Eppig, J. J. (2001) · Reproduction · doi:10.1530/rep.0.1220829 · Cited by 1,021
Control of Primordial Follicle Recruitment by Anti-Müllerian Hormone in the Mouse Ovary1
Durlinger, A. L. L., Kramer, P., Karels, B., de Jong, F. H., Uilenbroek, J. T. J., Grootegoed, J. A., & Themmen, A. P. N. (1999) · Endocrinology · doi:10.1210/endo.140.12.7204 · Cited by 1,011
Yan, C., Wang, P., DeMayo, J. L., DeMayo, F. J., Elvin, J. A., Cariño, C., Prasad, S. V., Skinner, S. M., Dunbar, B. S., Dube, J. L., et al. (2001) · Molecular Endocrinology · doi:10.1210/me.15.6.854 · Cited by 835
Metadata
- Authors
- Hayashi, M., McGee, E. A., Min, G., Klein, C., Rose, U. M., van Duin, M., & Hsueh, A. J. W.
- Venue
- Endocrinology
- Publisher
- Oxford University Press
- Published
- 1999-03-01
- Volume
- 140
- Issue
- 3
- Pages
- 1236-1244
- ISSN
- 0013-7227 (ISSN-L)
- OpenAlex
- W2049004724
- Cited by
- 357
- References
- 0
- FWCI
- 23.16
- Type
- journal article
- Language
- en
- Open access
- closed
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- CoChat. (2026). Citation check: Recombinant Growth Differentiation Factor-9 (GDF-9) Enhances Growth and Differentiation of Cultured Early Ovarian Follicles. https://app.cochat.ai/papers/10.1210/en.140.3.1236
- The paper
- Hayashi, M., McGee, E. A., Min, G., Klein, C., Rose, U. M., van Duin, M., & Hsueh, A. J. W. (1999). Recombinant Growth Differentiation Factor-9 (GDF-9) Enhances Growth and Differentiation of Cultured Early Ovarian Follicles. Endocrinology. https://doi.org/10.1210/en.140.3.1236
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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