Regulatory Mechanism of Rat Preantral Follicular Development: Involvement of FSH, Thyroid Hormone and Growth Differentiation Factor-9.
Bibliographic record
Abstract
Hypothyroidism is associated with suppressed ovarian follicular growth and infertility, although the cellular and molecular mechanism(s) involved is not known. While FSH promotes growth of cultured follicles, this response is markedly enhanced by the presence of growth differentiation factor-9 (GDF-9) or Triiodothyronine (T3). In vivo studies have shown that the effect of thyroid hormone on FSH-induced follicular growth is specific to the preantral stage. While GDF-9 is required for FSH receptor (FSHR) expression in preantral follicles, whether this response is required for the FSH-T3 interaction during preantral growth is unclear. The objective in the present study is to assess the role of T3 in the regulation of preantral follicular growth and the cellular mechanism involved. Preantral follicles (diameter: 150-180 µm) isolated from ovaries of 14-day old rats were cultured in serum-free medium for various durations (0 - 60h) and concentrations of FSH (0 - 100 ng/ml) or T3 (0 - 10-8 M). FSHR mRNA abundance and 18S rRNA levels were determined by quantitative real-time PCR. GDF-9 Morpholino antisense oligos (GDF-9 MO, 10 µM) or its control (CTL MO, 10 µM) were injected into the oocyte and the follicles were cultured for 4 6 days ± FSH and/or T3. Apoptosis (TUNEL) and GDF-9 expression (IHC) were performed at the end of the culture period. T3 markedly enhanced FSH-induced preantral follicular growth during 4-days of culture. GDF-9 in the cultured follicles was predominantly immunolocalized in the oocyte and significant oocyte GDF-9 expression is associated with follicles with minimal or absence of apoptosis. Addition of T3 or FSH markedly increased GDF-9 mRNA abundance in 12-18h (P<0.05). Intra-oocyte injection of GDF-9 MO decreased oocyte GDF-9 expression and induced follicular apoptosis, as well as suppressed growth of preantral follicles cultured with FSH and T3 (P<0.001). Addition of GDF-9 (100 ng/ml) to the MO-treated follicles significantly prevented the decrease in preantral follicular growth (P<0.01). In addition, T3 significantly increased FSHR mRNA abundance in the presence but not absence of FSH at 36h of culture period (P<0.001). Maximal responses were observed at 10 ng/ml FSH and 10-9 M T3. The level of FSHR mRNA was significantly decreased in GDF-9 MO-injected follicles cultured for 36h with both FSH and T3 (P<0.001). Our findings suggest that T3 plays an important role in the regulation of ovarian follicular growth. It interacts with FSH in promoting preantral follicular growth and this action is mediated through increased FSHR expression which in turn is dependent on adequate oocyte GDF-9 expression and action. This study offers new insight into the molecular and cellular mechanism of impaired follicular growth during hypothyroid state. (Supported by CIHR-IHDCYH Program on Oocyte Health and STIRRHS).
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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 | 0.000 | 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".