title: Linkage of regulators of TGF-β activity in the fetal ovary to polycystic ovary syndrome.
abstract: Although not often discussed, the ovaries of women with polycystic ovary syndrome (PCOS) show all the hallmarks of increased TGF-β activity, with increased amounts of fibrous tissue and collagen in the ovarian capsule or tunica albuginea and ovarian stroma. Recent studies suggest that PCOS could have fetal origins. Genetic studies of PCOS have also found linkage with a microsatellite located in intron 55 of the extracellular matrix protein fibrillin 3. Fibrillins regulate TGF-β bioactivity in tissues by binding latent TGF-β binding proteins. We therefore examined expression of fibrillins 1-3, latent TGF-β binding proteins 1-4, and TGF-β 1-3 in bovine and human fetal ovaries at different stages of gestation and in adult ovaries. We also immunolocalized fibrillins 1 and 3. The results indicate that TGF-β pathways operate during ovarian fetal development, but most important, we show fibrillin 3 is present in the stromal compartments of fetal ovaries and is highly expressed at a critical stage early in developing human and bovine fetal ovaries when stroma is expanding and follicles are forming. These changes in expression of fibrillin 3 in the fetal ovary could lead to a predisposition to develop PCOS in later life.
authors.affiliation: Research Centre for Reproductive Health, Discipline of Obstetrics and Gynaecology, Robinson Institute, University of Adelaide, SA, 5005, Australia.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Hatzirodos
authors.forename: Rosemary A
authors.initials: RA
authors.lastname: Bayne
authors.forename: Helen F
authors.initials: HF
authors.lastname: Irving-Rodgers
authors.forename: Katja
authors.initials: K
authors.lastname: Hummitzsch
authors.forename: Laetitia
authors.initials: L
authors.lastname: Sabatier
authors.forename: Sam
authors.initials: S
authors.lastname: Lee
authors.forename: Wendy
authors.initials: W
authors.lastname: Bonner
authors.forename: Mark A
authors.initials: MA
authors.lastname: Gibson
authors.forename: William E
authors.initials: WE
authors.lastname: Rainey
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Carr
authors.forename: Helen D
authors.initials: HD
authors.lastname: Mason
authors.forename: Dieter P
authors.initials: DP
authors.lastname: Reinhardt
authors.forename: Richard A
authors.initials: RA
authors.lastname: Anderson
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Rodgers
mesh_terms: D000818:Animals; D002417:Cattle; D005260:Female; D000071837:Fibrillins; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007150:Immunohistochemistry; D053779:Latent TGF-beta Binding Proteins / Q000235:genetics / Q000378:metabolism; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D006080:Ovarian Follicle / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D010053:Ovary / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D011085:Polycystic Ovary Syndrome / Q000235:genetics* / Q000378:metabolism; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D053781:Transforming Growth Factor beta2 / Q000235:genetics / Q000378:metabolism; D053782:Transforming Growth Factor beta3 / Q000235:genetics / Q000378:metabolism
chemical_list: C493782:FBN3 protein, human; D000071837:Fibrillins; D053779:Latent TGF-beta Binding Proteins; D008840:Microfilament Proteins; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D053782:Transforming Growth Factor beta3