254. Evidences for a novel cAMP-phosphodiesterase expressed in the bovine ovarian follicle
Bibliographic record
Abstract
3′5’-Cyclic adenosine monophosphate (cAMP) is an important second messenger in the mammalian ovarian follicle implicated in gonadotrophin signalling as well as oocyte meiotic arrest. Cyclic AMP-degrading phosphodiesterases (PDE) modulate cAMP levels in the ovarian follicle, but the specific PDE subtypes responsible for this degradation in the different cellular compartments within the bovine follicle remain unknown. The current dogma, established principally in rodent, presents PDE3A as the ‘oocyte PDE’, while PDE4D is the ‘granulosa/cumulus PDE’. Our PDE activity measurements suggested that a PDE3 (cilostamide-sensitive, 10µM) was representing 79% of the total cAMP-PDE activity in the bovine oocyte, in agreement with the dogma. However, our results suggested that PDE4 (rolipram-sensitive, 10µM) is representing only 19% of the cAMP-PDE activity in the cumulus cells, while 65% of the activity was due to PDE8 (IBMX-insensitive, 500µM), a result in direct opposition with the accepted PDE distribution in the ovarian follicle. Mural granulosa cells were displaying equal amounts of PDE4 (31%) and PDE8 (30%) cAMP-PDE activities. Interestingly, cAMP-PDE activities were not varying during the first 9 h of IVM in the bovine cumulus-oocyte complexes (COC), as seen in rat. COCs treated with an adenylyl cyclase stimulator (forkolin 100µM) in combinaison with the only known inhibitor for the PDE8 family, dipyridamole, are showing a dose-dependant increase of cAMP levels and a significant delay nuclear maturation, whereas a potent PDE4 inhibitor, rolipram (up to 100µM), was ineffective. This study provides the first insight into subtype-specific PDE cAMP degrading activities in the bovine ovarian follicle, especially around oocyte nuclear maturation. It demonstrates dramatic differential PDE subtype compartmentalisation between ovarian somatic cells and the germ cell, including the important contribution of a new PDE family member in the ovarian follicle, PDE8. PDE8 could be a novel pharmacological target to improve bovine oocyte IVM conditions and to increase developmental competence.
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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 | 0.002 |
| 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".