Expression of Fibrillins, Latent TGFbeta Binding Proteins and TGFbetas in the Bovine Fetal Ovary.
Notice bibliographique
Résumé
Polycystic ovary syndrome (PCOS) is the commonest endocrine condition affecting women of reproductive age with an incidence of 5-7% in Western societies. It is characterised by hyperandrogenaemia and hirsutism, chronic anovulation and polycystic ovaries. The ovaries of women with PCOS show the hallmarks of increased TGFbeta activity with increased amounts of fibrous tissue and collagen in the ovarian capsule or tunica albuginea, and ovarian stroma. Even the stromal theca interna is altered in PCOS with an elevated capacity to produce steroid hormones. In addition, androgenisation of the fetus leads to PCOS later in later life, suggesting that PCOS could have a fetal origin. There is also evidence of a genetic predisposition to PCOS, and genetic studies of PCOS have found linkage with a microsatellite located in intron 55 of the extracellular matrix protein, fibrillin 3. Fibrillins regulate TGFbeta bioactivity in tissues by binding latent TGFbeta binding proteins. Since little is known about TGFbeta bioactivity in the fetal ovaries in any species, we examined expression of fibrillins (FBN) 1, 2 and 3, latent TGFbeta binding proteins (LTBPs) 1, 2, 3 and 4, and TGFbeta 1, 2 and 3 in bovine fetal ovaries during gestation and compared them to adult stroma/tunica using real time RT-PCR [n = 8, 11, 9 and 5-8 for whole ovaries from the fetuses with crown-rump length of < 30, 30-60, and > 60 cm (estimated as < 125, 125-194, > 194 days of gestation age) and adult ovarian tunica/cortex, respectively]. FBN3 was highly expressed in the first trimester and then declined during gestation to reach very low levels in adult ovaries. The expression levels of FBN3 were as high as FBN1 and 2 in the first trimester. LTBP1, 3 and 4 were expressed during gestation. LTBP1 and 2 were substantially higher in adult ovaries than fetal ovaries. TGFBs expression levels were relatively uniform in the gestational groups. We also immunolocalised fibrillins 1 and 3. Ovaries from 12 fetuses of 13- 80 cm (86 - 241 days of gestation) were examined for fibrillin 1 which localised to fibres in the fetal ovarian stromal. Ovaries from 17 fetuses of a size range from 11.5 cm - 104 cm (82 - 296 days of gestation) and 8 adult ovaries were examined for fibrillin 3. Early in development fibrillin 3 localised to fibres in the stroma between ovigerous cords and nests of oognia. Staining for fibrillin 3 was more intense in first trimester ovaries and fainter or not detectable at later stages or in adult ovaries. These results indicate that TGFbeta pathways are present in the fetal ovary. Importantly we have shown that fibrillin 3 is present in the stromal compartments of fetal ovaries and is highly expressed at a critical stage early when stroma is expanding and follicles are forming. Altered expression of fibrillin 3 during development of the fetal ovary could predispose an individual to PCOS in later life by causing an increased deposition of ovarian stromal matrix. This study therefore heralds a role for fibrillins and LTBPs in regulating the activity of TGFbetas in the development of the stromal compartments of the normal and PCOS ovary. It also links previous genetic data implicating fibrillin 3 with a physiological mechanism, in line with animal models and clinical observations, of a fetal predisposition to development of PCOS in adulthood. Funding provided by the National Health and Medical Research Council of Australia. (poster)
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».