The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

BMP15  -  bone morphogenetic protein 15

Homo sapiens

Synonyms: BMP-15, Bone morphogenetic protein 15, GDF-9B, GDF9B, Growth/differentiation factor 9B, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of BMP15


High impact information on BMP15

  • Whereas BMP15 is a member of the transforming growth factor beta (TGFbeta) superfamily and is specifically expressed in oocytes, its function is unknown [1].
  • These findings establish that BMP15 is essential for female fertility and that natural mutations in an ovary-derived factor can cause both increased ovulation rate and infertility phenotypes in a dosage-sensitive manner [1].
  • BMP15 is an oocyte-specific growth/differentiation factor that stimulates folliculogenesis and granulosa cell (GC) growth [4].
  • Bone morphogenetic protein-15 (BMP-15) and growth and differentiation factor-9 (GDF-9) are members of the transforming growth factor-beta superfamily [5].
  • Here we have established a series of cell lines, which express recombinant BMP-15, GDF-9, or both, and investigated whether they form homodimers and/or heterodimers [5].

Biological context of BMP15

  • Although spontaneous in vitro oocyte maturation occurred normally, oocyte fertilization and preimplantation embryogenesis were significantly altered in the DM, suggesting that the full complement of both GDF9 and BMP15 are essential for the development and function of oocytes [6].
  • The granulosa cell receptor which mediates the BMP15 response has not yet been identified, but the discovery that a point mutation in the BMP1B receptor in Booroola sheep is responsible for increased ovulation rate highlights the importance of the TGFbeta signalling molecules in early folliculogenesis [7].
  • However, three single nucleotide polymorphisms in the BMP15 gene, two in the 5' untranslated region (31T>G and 71C>G) and another in exon 1 (387G>A), were found to be common in both POF and control groups [8].
  • From examination of inherited patterns of ovulation rate in sheep, point mutations have been identified in two oocyte-expressed genes, BMP15 (GDF9B) and GDF9 [9].
  • Missense mutations in the BMP15 gene are associated with ovarian failure [10].

Anatomical context of BMP15

  • BMP15 alone, GDF9 alone or the two combined all (P<0.05) increased the proportion of oocytes that reached the blastocyst stage post-insemination from 41% (controls) to 58%, 50% and 55%, respectively [11].
  • Strong BMP15 immunostaining was observed in the follicular fluid of atretic antral follicles after FSH treatment and in expanded, but not in compact, cumulus cells after hCG [12].
  • Thus, since the mRNAs encoding GDF9 and BMP15 were not observed until follicular formation, it is unlikely that these proteins have any role in early germ cell development [13].
  • To define the function of BMP-15 in mice, we generated embryonic stem cells and knockout mice, which have a null mutation in this X-linked gene [14].

Associations of BMP15 with chemical compounds

  • Moreover, it identifies the stimulation of GC proliferation and the differential regulation of two crucial steroid hormones as the first biological functions of BMP-15 [15].

Other interactions of BMP15


Analytical, diagnostic and therapeutic context of BMP15

  • Animal models showed the important role in female reproduction played by the product of a gene located at Xp11.2 in humans (BMP15) [4].
  • The human GDF-9B transcript can be detected only in the gonads by RT-PCR analysis, and in situ hybridization studies indicate that it is not expressed in small primary follicles but, rather, in the oocytes of late primary follicles [20].
  • The present case-control study has been structured to establish the role of BMP15 germline status associated with ovarian failure [10].
  • Sequence analysis of the coding region of the BMP15 gene was carried out in a cohort of women with POF (n=133), primary amenorrhoea (n=60), and secondary amenorrhoea (n=9) compared with control females (n=197) [10].
  • We demonstrate, through a combination of Northern blot and in situ hybridization analyses, that mouse Bmp15 is expressed specifically in the oocyte beginning at the one-layer primary follicle stage and continuing through ovulation [21].


  1. Mutations in an oocyte-derived growth factor gene (BMP15) cause increased ovulation rate and infertility in a dosage-sensitive manner. Galloway, S.M., McNatty, K.P., Cambridge, L.M., Laitinen, M.P., Juengel, J.L., Jokiranta, T.S., McLaren, R.J., Luiro, K., Dodds, K.G., Montgomery, G.W., Beattie, A.E., Davis, G.H., Ritvos, O. Nat. Genet. (2000) [Pubmed]
  2. Bone morphogenetic protein 15 (BMP15) alleles predict over-response to recombinant follicle stimulation hormone and iatrogenic ovarian hyperstimulation syndrome (OHSS). Morón, F.J., de Castro, F., Royo, J.L., Montoro, L., Mira, E., Sáez, M.E., Real, L.M., González, A., Mañes, S., Ruiz, A. Pharmacogenet. Genomics (2006) [Pubmed]
  3. A unique preovulatory expression pattern plays a key role in the physiological functions of BMP-15 in the mouse. Yoshino, O., McMahon, H.E., Sharma, S., Shimasaki, S. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  4. Hypergonadotropic ovarian failure associated with an inherited mutation of human bone morphogenetic protein-15 (BMP15) gene. Di Pasquale, E., Beck-Peccoz, P., Persani, L. Am. J. Hum. Genet. (2004) [Pubmed]
  5. Effect of intracellular interactions on the processing and secretion of bone morphogenetic protein-15 (BMP-15) and growth and differentiation factor-9. Implication of the aberrant ovarian phenotype of BMP-15 mutant sheep. Liao, W.X., Moore, R.K., Otsuka, F., Shimasaki, S. J. Biol. Chem. (2003) [Pubmed]
  6. Synergistic roles of BMP15 and GDF9 in the development and function of the oocyte-cumulus cell complex in mice: genetic evidence for an oocyte-granulosa cell regulatory loop. Su, Y.Q., Wu, X., O'Brien, M.J., Pendola, F.L., Denegre, J.N., Matzuk, M.M., Eppig, J.J. Dev. Biol. (2004) [Pubmed]
  7. Bmp15 mutations and ovarian function. Galloway, S.M., Gregan, S.M., Wilson, T., McNatty, K.P., Juengel, J.L., Ritvos, O., Davis, G.H. Mol. Cell. Endocrinol. (2002) [Pubmed]
  8. Mutational analysis of BMP15 and GDF9 as candidate genes for premature ovarian failure. Chand, A.L., Ponnampalam, A.P., Harris, S.E., Winship, I.M., Shelling, A.N. Fertil. Steril. (2006) [Pubmed]
  9. The oocyte and its role in regulating ovulation rate: a new paradigm in reproductive biology. McNatty, K.P., Moore, L.G., Hudson, N.L., Quirke, L.D., Lawrence, S.B., Reader, K., Hanrahan, J.P., Smith, P., Groome, N.P., Laitinen, M., Ritvos, O., Juengel, J.L. Reproduction (2004) [Pubmed]
  10. Missense mutations in the BMP15 gene are associated with ovarian failure. Dixit, H., Rao, L.K., Padmalatha, V.V., Kanakavalli, M., Deenadayal, M., Gupta, N., Chakrabarty, B., Singh, L. Hum. Genet. (2006) [Pubmed]
  11. Oocyte-secreted factors enhance oocyte developmental competence. Hussein, T.S., Thompson, J.G., Gilchrist, R.B. Dev. Biol. (2006) [Pubmed]
  12. Oocyte Bone Morphogenetic Protein 15, but not Growth Differentiation Factor 9, Is Increased During Gonadotropin-Induced Follicular Development in the Immature Mouse and Is Associated with Cumulus Oophorus Expansion. Gu??ripel, X., Brun, V., Gougeon, A. Biol. Reprod. (2006) [Pubmed]
  13. Expression of mRNA encoding growth differentiation factor 9 and bone morphogenetic protein 15 during follicular formation and growth in a marsupial, the brushtail possum (Trichosurus vulpecula). Eckery, D.C., Whale, L.J., Lawrence, S.B., Wylde, K.A., McNatty, K.P., Juengel, J.L. Mol. Cell. Endocrinol. (2002) [Pubmed]
  14. Synergistic roles of bone morphogenetic protein 15 and growth differentiation factor 9 in ovarian function. Yan, C., Wang, P., DeMayo, J., DeMayo, F.J., Elvin, J.A., Carino, C., Prasad, S.V., Skinner, S.S., Dunbar, B.S., Dube, J.L., Celeste, A.J., Matzuk, M.M. Mol. Endocrinol. (2001) [Pubmed]
  15. Bone morphogenetic protein-15. Identification of target cells and biological functions. Otsuka, F., Yao, Z., Lee, T., Yamamoto, S., Erickson, G.F., Shimasaki, S. J. Biol. Chem. (2000) [Pubmed]
  16. The human cumulus--oocyte complex gene-expression profile. Assou, S., Anahory, T., Pantesco, V., Le Carrour, T., Pellestor, F., Klein, B., Reyftmann, L., Dechaud, H., De Vos, J., Hamamah, S. Hum. Reprod. (2006) [Pubmed]
  17. The activin-follistatin system and in vitro early follicle development in goats. Silva, J.R., Tharasanit, T., Taverne, M.A., van der Weijden, G.C., Santos, R.R., Figueiredo, J.R., van den Hurk, R. J. Endocrinol. (2006) [Pubmed]
  18. Novel variants in growth differentiation factor 9 in mothers of dizygotic twins. Palmer, J.S., Zhao, Z.Z., Hoekstra, C., Hayward, N.K., Webb, P.M., Whiteman, D.C., Martin, N.G., Boomsma, D.I., Duffy, D.L., Montgomery, G.W. J. Clin. Endocrinol. Metab. (2006) [Pubmed]
  19. Highly prolific Booroola sheep have a mutation in the intracellular kinase domain of bone morphogenetic protein IB receptor (ALK-6) that is expressed in both oocytes and granulosa cells. Wilson, T., Wu, X.Y., Juengel, J.L., Ross, I.K., Lumsden, J.M., Lord, E.A., Dodds, K.G., Walling, G.A., McEwan, J.C., O'Connell, A.R., McNatty, K.P., Montgomery, G.W. Biol. Reprod. (2001) [Pubmed]
  20. Human growth differentiation factor 9 (GDF-9) and its novel homolog GDF-9B are expressed in oocytes during early folliculogenesis. Aaltonen, J., Laitinen, M.P., Vuojolainen, K., Jaatinen, R., Horelli-Kuitunen, N., Seppä, L., Louhio, H., Tuuri, T., Sjöberg, J., Bützow, R., Hovata, O., Dale, L., Ritvos, O. J. Clin. Endocrinol. Metab. (1999) [Pubmed]
  21. The bone morphogenetic protein 15 gene is X-linked and expressed in oocytes. Dube, J.L., Wang, P., Elvin, J., Lyons, K.M., Celeste, A.J., Matzuk, M.M. Mol. Endocrinol. (1998) [Pubmed]
WikiGenes - Universities