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Gene Review

Gdf9  -  growth differentiation factor 9

Mus musculus

Synonyms: GDF-9, Gdf-9, Growth/differentiation factor 9
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Disease relevance of Gdf9


High impact information on Gdf9


Biological context of Gdf9


Anatomical context of Gdf9

  • After 24 h of culture in the presence of 0.5 IU/ml of FSH, cumulus shells cocultured with buffer- and Bmp15 dsRNA-injected oocytes exhibited a high degree of expansion, whereas cumulus shells cocultured with Gdf9 dsRNA-injected oocytes exhibited only limited expansion [6].
  • GCNF-dependent repression of BMP-15 and GDF-9 mediates gamete regulation of female fertility [2].
  • Integrin alpha(v) mRNA is most highly expressed in the granulosa cells of multilayer growing follicles, and therefore only low levels of expression are detectable in the Gdf 9 knockout ovaries [8].
  • The major findings of our studies are as follows: 1) There are no detectable signals around GDF-9-deficient follicles for several theca cell layer markers [i.e. 17alpha-hydroxylase, LH receptor (LHR), and c-kit, the receptor for kit ligand] [5].
  • Up-regulation of kit ligand, via signaling through c-kit on the oocyte, may be directly involved in the increased size of GDF-9-deficient oocytes and the eventual demise of the oocyte; 3) After loss of the oocyte, the cells of the GDF-9-deficient follicles remain in a steroidogenic cluster that histologically resembles small corpora lutea [5].

Associations of Gdf9 with chemical compounds


Regulatory relationships of Gdf9


Other interactions of Gdf9

  • Thus, Brd2 expression appears to correlate with stages of oocyte maturation, independent of FSH or GDF9 action and the subsequent disruption in normal follicle development in these models [10].
  • These same expression patterns were also seen in oocytes from Gdf9(-/-) and Fshb(-/-) mice [10].
  • Knockout of pentraxin 3, a downstream target of growth differentiation factor-9, causes female subfertility [4].
  • Based on knockout mouse models BMP-6 does not play an essential role in ovarian function, but GDF-9 is absolutely required for preantral follicle development [11].
  • To investigate the role of GDF9 in cumulus expansion, two endpoints were used to evaluate cumulus expansion: Has2 and Ptgs2 mRNA levels were measured in cumulus cells using real-time RT-PCR, and assessment of cumulus expansion was undertaken morphologically [6].

Analytical, diagnostic and therapeutic context of Gdf9


  1. Paracrine actions of growth differentiation factor-9 in the mammalian ovary. Elvin, J.A., Clark, A.T., Wang, P., Wolfman, N.M., Matzuk, M.M. Mol. Endocrinol. (1999) [Pubmed]
  2. GCNF-dependent repression of BMP-15 and GDF-9 mediates gamete regulation of female fertility. Lan, Z.J., Gu, P., Xu, X., Jackson, K.J., DeMayo, F.J., O'Malley, B.W., Cooney, A.J. EMBO J. (2003) [Pubmed]
  3. Growth differentiation factor-9 stimulates progesterone synthesis in granulosa cells via a prostaglandin E2/EP2 receptor pathway. Elvin, J.A., Yan, C., Matzuk, M.M. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  4. Knockout of pentraxin 3, a downstream target of growth differentiation factor-9, causes female subfertility. Varani, S., Elvin, J.A., Yan, C., DeMayo, J., DeMayo, F.J., Horton, H.F., Byrne, M.C., Matzuk, M.M. Mol. Endocrinol. (2002) [Pubmed]
  5. Molecular characterization of the follicle defects in the growth differentiation factor 9-deficient ovary. Elvin, J.A., Yan, C., Wang, P., Nishimori, K., Matzuk, M.M. Mol. Endocrinol. (1999) [Pubmed]
  6. RNA interference evidence that growth differentiation factor-9 mediates oocyte regulation of cumulus expansion in mice. Gui, L.M., Joyce, I.M. Biol. Reprod. (2005) [Pubmed]
  7. A novel growth differentiation factor-9 (GDF-9) related factor is co-expressed with GDF-9 in mouse oocytes during folliculogenesis. Laitinen, M., Vuojolainen, K., Jaatinen, R., Ketola, I., Aaltonen, J., Lehtonen, E., Heikinheimo, M., Ritvos, O. Mech. Dev. (1998) [Pubmed]
  8. Characterization of integrin expression in the mouse ovary. Burns, K.H., Owens, G.E., Fernandez, J.M., Nilson, J.H., Matzuk, M.M. Biol. Reprod. (2002) [Pubmed]
  9. Interplay between paracrine signaling and gap junctional communication in ovarian follicles. Gittens, J.E., Barr, K.J., Vanderhyden, B.C., Kidder, G.M. J. Cell. Sci. (2005) [Pubmed]
  10. Bromodomain containing 2 (Brd2) is expressed in distinct patterns during ovarian folliculogenesis independent of FSH or GDF9 action. Trousdale, R.K., Wolgemuth, D.J. Mol. Reprod. Dev. (2004) [Pubmed]
  11. Oocyte-expressed TGF-beta superfamily members in female fertility. Elvin, J.A., Yan, C., Matzuk, M.M. Mol. Cell. Endocrinol. (2000) [Pubmed]
  12. Growth differentiation factor 9 regulates expression of the bone morphogenetic protein antagonist gremlin. Pangas, S.A., Jorgez, C.J., Matzuk, M.M. J. Biol. Chem. (2004) [Pubmed]
  13. Role of oocyte-secreted growth differentiation factor 9 in the regulation of mouse cumulus expansion. Dragovic, R.A., Ritter, L.J., Schulz, S.J., Amato, F., Armstrong, D.T., Gilchrist, R.B. Endocrinology (2005) [Pubmed]
  14. Immunoneutralization of growth differentiation factor 9 reveals it partially accounts for mouse oocyte mitogenic activity. Gilchrist, R.B., Ritter, L.J., Cranfield, M., Jeffery, L.A., Amato, F., Scott, S.J., Myllymaa, S., Kaivo-Oja, N., Lankinen, H., Mottershead, D.G., Groome, N.P., Ritvos, O. Biol. Reprod. (2004) [Pubmed]
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