TY - JOUR
T1 - Linkage of regulators of TGF-β activity in the fetal ovary to polycystic ovary syndrome
AU - Hatzirodos, Nicholas
AU - Bayne, Rosemary A.
AU - Irving-Rodgers, Helen F.
AU - Hummitzsch, Katja
AU - Sabatier, Laetitia
AU - Lee, Sam
AU - Bonner, Wendy
AU - Gibson, Mark A.
AU - Rainey, William E.
AU - Carr, Bruce R.
AU - Mason, Helen D.
AU - Reinhardt, Dieter P.
AU - Anderson, Richard A.
AU - Rodgers, Raymond J.
PY - 2011/7
Y1 - 2011/7
N2 - 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.
AB - 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.
KW - Fibrillin
KW - Latent transforming growth factor-β binding protein
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U2 - 10.1096/fj.11-181099
DO - 10.1096/fj.11-181099
M3 - Article
C2 - 21411746
AN - SCOPUS:79960162693
SN - 0892-6638
VL - 25
SP - 2256
EP - 2265
JO - FASEB Journal
JF - FASEB Journal
IS - 7
ER -