Receptor tyrosine kinases in granulosa cells of ovulating follicles in mice
Bibliographic record
Abstract
Successful expulsion of a fertilizable oocyte from follicles, ovulation, requires the actions of extracellular and intracellular signals including those mediated by receptor tyrosine kinases (RTKs) and growth factors.The activation of the epidermal growth factor receptor (Egfr) has been well established during ovulation induced by the preovulatory surge of luteinizing hormone (LH).However, potential roles for other RTKs and their respective growth factors have not been thoroughly studied during ovulation.Therefore, the aim of this project was to analyze growth factor signaling induced by LH in mouse granulosa cells of ovulating follicles.Granulosa cell samples were collected from immature mice, superstimulated with equine chorionic gonadotropin (eCG) and human chorionic gonadotropin (hCG) at 48h apart.We used the Mouse Phospho-RTK Array Kit to systematically catalogue the RTKs that are activated by LH signaling.There was an increase in phosphorylation of fibroblast growth factor receptor 2 (Fgfr2) and ephrin receptor B1 (EphB1) in granulosa cells at 4h post-hCG when compared to 0h hCG.We measured the expression of the genes encoding Fgfr isoforms and EphB1 along with their respective ligands.The relative mRNA abundance of the receptors did not change upon hCG treatment.However, transcript levels of their respective ligands, fibroblast growth factor 2 (Fgf2) and ephrin-B1 (Efnb1), increased significantly at 4h post-hCG.We also found that protein abundance of Fgf2 increased at hCG4h.Further qPCR analyses revealed that increased Fgf2 expression was associated with decreased mRNA abundance of Spry3, a member of the Sprouty family of proteins known to inhibit FGF signaling.Finally, intraperitoneal treatment with two Fgfr inhibitors (AZD4547 or BGJ398) did not alter ovulation rate when compared to vehicle treatment.Taken together, the present study investigated two RTK pathways in granulosa cells of preovulatory ovulating follicles in mice.The ovulatory stimulus with hCG induces the expression of the ligands Fgf2 and Efnb1 in association with increased phosphorylation of their respective receptors, Fgfr2 IIIC and Ephb1 in granulosa cells.However, FGF and ephrin pathways do not appear to be obligatory for ovulation.Their temporal association with luteinization suggests that they may participate in the formation of the CL, which require further investigation.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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".