title: Impaired production of BMP-15 and GDF-9 mature proteins derived from proproteins WITH mutations in the proregion.
abstract: Mutations in the bone morphogenetic protein-15 (BMP-15) and growth and differentiation factor-9 (GDF-9) genes have been identified in women with primary ovarian insufficiency (POI) and mothers of dizygotic twins. Here, we show that biological activities of the conditioned media from human embryonic kidney 293F cells transfected with two representative BMP-15 and GDF-9 mutants identified in the affected women have significantly reduced biological activities compared with the corresponding wild-type. Moreover, this difference is due to decreased production of the mature proteins, attributed most likely to impaired posttranslational processing of the proprotein. As genetic studies of the BMP-15 and/or GDF-9 genes in ewes established that a reduction of these proteins is associated with an increased ovulation rate, it is conceivable that women affected with these mutations may have an increased probability of bearing dizygotic twins during active reproductive ages before diagnosis with POI at later ages due to an earlier exhaustion of ovarian reserve.
authors.affiliation: Department of Reproductive Medicine, University of California San Diego, School of Medicine, 9500 Gilman Dr., La Jolla, CA 92093-0633, United States.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Inagaki
authors.forename: Shunichi
authors.initials: S
authors.lastname: Shimasaki
mesh_terms: D000818:Animals; D055430:Bone Morphogenetic Protein 15 / Q000235:genetics* / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D055429:Growth Differentiation Factor 9 / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D051379:Mice; D017354:Point Mutation; D016649:Primary Ovarian Insufficiency / Q000235:genetics; D014176:Protein Biosynthesis / Q000235:genetics; D055503:Protein Multimerization / Q000235:genetics; D011498:Protein Precursors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000235:genetics; D021382:Protein Sorting Signals / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D055430:Bone Morphogenetic Protein 15; D055429:Growth Differentiation Factor 9; D011498:Protein Precursors; D021382:Protein Sorting Signals