Expression of Fibrillins, Latent TGFbeta Binding Proteins and TGFbetas in the Bovine Fetal Ovary.
Bibliographic record
Abstract
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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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".