The Extracellular Matrix Protein, Spondin 1, Regulates Proliferation, Survival, and Adhesion of Granulosa Cells.
Bibliographic record
Abstract
It is well established that dramatic changes in the composition of the ovarian extracellular matrix (ECM) and cell-cell adhesion proteins occur throughout folliculogenesis. The ECM protein, Spondin 1 (F-spondin), is a secreted adhesion protein that regulates patterning of the developing nervous system by promoting outgrowth and adhesion of axons, and inhibiting adhesion of neural crest cells. SPON1 also enhances neuroblastoma cell survival under adverse conditions. SPON1 has been previously identified in bovine follicular fluid and is highly expressed in the human ovary. However, a function for SPON1 within the ovary and its regulation by gonadotropins has not been studied. Previous global gene expression analysis indicated that Spon1 mRNA levels increased in granulosa cells isolated from PMSG-treated prepubertal mice but not vehicle-treated mice, suggesting that SPON1 expression is regulated by FSH, and that SPON1 may play a role in folliculogenesis. The objectives of our study were to: a) characterize the expression and localization of Spon1 in the mouse ovary, and b) identify what function SPON1 may play within granulosa cells of the ovary. Using quantitative RT-PCR, we confirmed that Spon1 mRNA levels increased 5-fold in granulosa cells isolated from mice treated with PMSG for 48h compared to vehicle-treated controls, indicating that FSH increases Spon1 expression. Immunofluorescence studies localized SPON1 to regions between and surrounding both theca and granulosa cells of follicles of various sizes, from small secondary to preovulatory follicles. We have also discovered several potential roles for Spondin 1 in granulosa cell function. First, using a colorimetric viability assay, we found that recombinant human Spondin 1 (rhSPON1) enhanced the viability and/or proliferation of KGN human granulosa cells up to 30% compared to vehicle-treated cells, suggesting that SPON1 regulates granulosa cell viability and/or proliferation. Similarly, in primary mouse granulosa cells cultured in serum-free medium, rhSPON1 protected against loss of granulosa cell viability that occurs under these conditions. Addition of rhSPON1 enhanced granulosa cell viability by up to 50% compared to vehicle-treated controls, suggesting again that SPON1 may regulate granulosa cell viability during folliculogenesis. Finally, rhSPON1 induced clumping of primary mouse granulosa cells, suggesting a role for Spondin1 in granulosa cell adhesion, as has been reported in rhSPON1-treated neural cells. In summary, we have shown for the first time that the ECM protein, SPON1, regulates granulosa cell viability/proliferation, survival, and cell-cell adhesion, and therefore may play a previously-unidentified role in mammalian folliculogenesis and fertility. (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 | 0.002 | 0.001 |
| 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 | 0.001 |
| 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".