title: BMP system expression in GCs from polycystic ovary syndrome women and the in vitro effects of BMP4, BMP6, and BMP7 on GC steroidogenesis.
abstract: BACKGROUND
  The bone morphogenetic proteins (BMPs) are growth factors involved in the folliculogenesis. Alteration in their expression may compromise the reproductive process in disease such as the polycystic ovary syndrome (PCOS). This study investigated the expression and role of granulosa cell (GC) BMP from normal cycling and PCOS women.
  
  
  RESULTS
  This prospective study was performed in GCs obtained from 14 patients undergoing IVF: i) six women with normal ovulatory cycles and tubal or male infertility and ii) eight women with PCOS. BMP2, BMP4, BMP5, BMP6, BMP7, and BMP8A and their receptors BMPR1A, BMPR1B, and BMPR2 were identified by RT-PCR in GCs from normally cycling and PCOS women. BMP4, BMP6, and BMP7 expressions were confirmed by immunohistochemistry. Quantitative transcript analysis showed the predominant expression of BMP6. In GCs from PCOS women, an overexpression of BMP6 (P<0.01) and BMPR1A mRNA (P<0.05) was observed. GC culture experiments demonstrated that basal estradiol (E₂) production was threefold higher but FSH-induced E₂ increment was twofold lower in PCOS compared with controls. In PCOS, BMP6 and BMP7 exerted a stimulatory effect on basal E₂ production while BMP4 and BMP6 inhibited FSH-induced E₂ production. FSH receptor and aromatase expression were not different between both groups.
  
  
  CONCLUSIONS
  The BMP system is expressed in human GCs from normal cycling and PCOS women. The BMP may be involved in reproductive abnormalities found in PCOS.
authors.affiliation: Laboratoire, EA 2608, Université de Caen-Basse Normandie, F-14032 Caen Cedex, France.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Khalaf
authors.forename: Julia
authors.initials: J
authors.lastname: Morera
authors.forename: Antoine
authors.initials: A
authors.lastname: Bourret
authors.forename: Yves
authors.initials: Y
authors.lastname: Reznik
authors.forename: Christine
authors.initials: C
authors.lastname: Denoual
authors.forename: Michel
authors.initials: M
authors.lastname: Herlicoviez
authors.forename: Hervé
authors.initials: H
authors.lastname: Mittre
authors.forename: Annie
authors.initials: A
authors.lastname: Benhaim
mesh_terms: D000328:Adult; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics / Q000378:metabolism; D055418:Bone Morphogenetic Protein 6 / Q000235:genetics / Q000378:metabolism; D055419:Bone Morphogenetic Protein 7 / Q000235:genetics / Q000378:metabolism; D052004:Bone Morphogenetic Protein Receptors / Q000235:genetics / Q000378:metabolism*; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004958:Estradiol / Q000378:metabolism; D005260:Female; D043373:Follicle Stimulating Hormone, Human / Q000378:metabolism; D005786:Gene Expression Regulation; D006107:Granulosa Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D011085:Polycystic Ovary Syndrome / Q000378:metabolism* / Q000473:pathology; D011446:Prospective Studies; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013256:Steroids / Q000378:metabolism*; D055815:Young Adult
chemical_list: C525809:BMP4 protein, human; C525816:BMP6 protein, human; C525819:BMP7 protein, human; D055415:Bone Morphogenetic Protein 4; D055418:Bone Morphogenetic Protein 6; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D043373:Follicle Stimulating Hormone, Human; D020033:Protein Isoforms; D012333:RNA, Messenger; D013256:Steroids; D004958:Estradiol; D052004:Bone Morphogenetic Protein Receptors