Bone morphogenetic protein 15
Bone morphogenetic protein 15 is a protein that in humans is encoded by the BMP15 gene.[3][4] It's mainly involved in folliculogenesis.[5]
Structure and expression
The protein encoded by this gene is a member of the TGF-β superfamily. It is a paracrine signaling molecule involved in oocyte and follicular development. Using Northern blot analysis, BMP15 has been shown to be exclusively expressed in the ovaries. It is thought that this protein may be involved in oocyte maturation and follicular development as a homodimer or by forming heterodimers with a related protein, Gdf9.[4]
Functions
The functions of BMP15 include:[5]
- Promotion of growth and maturation of ovarian follicles, starting from the primary gonadotrophin-independent phases of folliculogenesis.
- Regulation of the sensitivity of granulosa cells to follicle-stimulating hormone (FSH) action, contributing to the determination of the number of eggs that are ovulated.
- Prevention of granulosa cell apoptosis.
- Promotion of developmental competence of oocytes.
Defects in BMP15 are associated with primary ovarian insufficiency. BMP15may represent a biomarker of ovarian response to ovarian stimulation or oocyte quality.[5]
References
- ↑ "Human PubMed Reference:".
- ↑ "Mouse PubMed Reference:".
- ↑ Dube JL, Wang P, Elvin J, Lyons KM, Celeste AJ, Matzuk MM (Feb 1999). "The bone morphogenetic protein 15 gene is X-linked and expressed in oocytes". Mol Endocrinol. 12 (12): 1809–17. PMID 9849956. doi:10.1210/me.12.12.1809.
- 1 2 "Entrez Gene: BMP15 bone morphogenetic protein 15".
- 1 2 3 Persani, L.; Rossetti, R.; Di Pasquale, E.; Cacciatore, C.; Fabre, S. (2014). "The fundamental role of bone morphogenetic protein 15 in ovarian function and its involvement in female fertility disorders". Human Reproduction Update. 20 (6): 869–883. ISSN 1355-4786. PMID 24980253. doi:10.1093/humupd/dmu036.
External links
- Human BMP15 genome location and BMP15 gene details page in the UCSC Genome Browser.
Further reading
- Aaltonen J, Laitinen MP, Vuojolainen K, et al. (1999). "Human growth differentiation factor 9 (GDF-9) and its novel homolog GDF-9B are expressed in oocytes during early folliculogenesis.". J. Clin. Endocrinol. Metab. 84 (8): 2744–50. PMID 10443672. doi:10.1210/jc.84.8.2744.
- Galloway SM, McNatty KP, Cambridge LM, et al. (2000). "Mutations in an oocyte-derived growth factor gene (BMP15) cause increased ovulation rate and infertility in a dosage-sensitive manner.". Nat. Genet. 25 (3): 279–83. PMID 10888873. doi:10.1038/77033.
- Otsuka F, Yao Z, Lee T, et al. (2001). "Bone morphogenetic protein-15. Identification of target cells and biological functions.". J. Biol. Chem. 275 (50): 39523–8. PMID 10998422. doi:10.1074/jbc.M007428200.
- Otsuka F, Moore RK, Iemura S, et al. (2002). "Follistatin inhibits the function of the oocyte-derived factor BMP-15.". Biochem. Biophys. Res. Commun. 289 (5): 961–6. PMID 11741284. doi:10.1006/bbrc.2001.6103.
- Moore RK, Otsuka F, Shimasaki S (2003). "Molecular basis of bone morphogenetic protein-15 signaling in granulosa cells.". J. Biol. Chem. 278 (1): 304–10. PMID 12419820. doi:10.1074/jbc.M207362200.
- Liao WX, Moore RK, Otsuka F, Shimasaki S (2003). "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.". J. Biol. Chem. 278 (6): 3713–9. PMID 12446716. doi:10.1074/jbc.M210598200.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. PMC 139241
. PMID 12477932. doi:10.1073/pnas.242603899. - Liao WX, Moore RK, Shimasaki S (2004). "Functional and molecular characterization of naturally occurring mutations in the oocyte-secreted factors bone morphogenetic protein-15 and growth and differentiation factor-9.". J. Biol. Chem. 279 (17): 17391–6. PMID 14970198. doi:10.1074/jbc.M401050200.
- Di Pasquale E, Beck-Peccoz P, Persani L (2004). "Hypergonadotropic ovarian failure associated with an inherited mutation of human bone morphogenetic protein-15 (BMP15) gene.". Am. J. Hum. Genet. 75 (1): 106–11. PMC 1181993 . PMID 15136966. doi:10.1086/422103.
- Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. PMC 528928 . PMID 15489334. doi:10.1101/gr.2596504.
- Ross MT, Grafham DV, Coffey AJ, et al. (2005). "The DNA sequence of the human X chromosome.". Nature. 434 (7031): 325–37. PMC 2665286 . PMID 15772651. doi:10.1038/nature03440.
- Hashimoto O, Moore RK, Shimasaki S (2005). "Posttranslational processing of mouse and human BMP-15: potential implication in the determination of ovulation quota.". Proc. Natl. Acad. Sci. U.S.A. 102 (15): 5426–31. PMC 556231 . PMID 15809424. doi:10.1073/pnas.0409533102.
- Dixit H, Rao LK, Padmalatha VV, et al. (2006). "Missense mutations in the BMP15 gene are associated with ovarian failure.". Hum. Genet. 119 (4): 408–15. PMID 16508750. doi:10.1007/s00439-006-0150-0.
- Laissue P, Christin-Maitre S, Touraine P, et al. (2006). "Mutations and sequence variants in GDF9 and BMP15 in patients with premature ovarian failure.". Eur. J. Endocrinol. 154 (5): 739–44. PMID 16645022. doi:10.1530/eje.1.02135.
- Chand AL, Ponnampalam AP, Harris SE, et al. (2006). "Mutational analysis of BMP15 and GDF9 as candidate genes for premature ovarian failure.". Fertil. Steril. 86 (4): 1009–12. PMID 17027369. doi:10.1016/j.fertnstert.2006.02.107.
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