Glycine-Dependent Cell Volume Control in Mouse Oocytes Is Activated at Ovulation Due to Release of Inhibition Mediated by the Intact Antral Follicle via Gap Junctions.
Bibliographic record
Abstract
Preimplantation embryos are extremely sensitive to perturbations of cell volume. For normal development, preimplantation mouse embryos up the to 4-cell stage require a mechanism of cell volume regulation unique to embryos, in which glycine is accumulated via the GLYT1 transporter to serve as an osmolyte in the embryo. This mechanism is not active in germinal vesicle stage (GV) oocytes within the follicle but is activated within 4 hours following the LH surge at ovulation. How GLYT1 is activated to initiate cell volume regulation during ovulation is unknown. We previously found that GLYT1 will spontaneously activate in GV oocytes removed from the follicle, independent of meiotic maturation. We have now found that the ability to activate GLYT1 when removed from the follicle develops during oocyte growth even though quiescence is normally maintained until ovulation. We thus hypothesize that an inhibitory factor maintains GLYT1 in an inactive state within the follicle. Consistent with this, GLYT1 remained quiescent in isolated intact antral follicles cultured for up to 24 hours. GLYT1 then became activated by 4 hours following removal of oocytes from cultured follicles, suggesting that the antral follicle is sufficient to maintain GLYT1 in an inactive state. GLYT1 activity developed, however, in isolated cumulus-oocyte complexes (COCs), implying that signaling from mural granulosa may be required. To test whether functional gap junctional communication is required for this signal, intact antral follicles were incubated for 10 hours with or without several gap junction uncouplers and GLYT1 activity measured in oocytes immediately after isolation from the follicle. In the presence of gap junction uncouplers, GLYT1 became fully activated in oocytes while within the antral follicle. It has been found that naturietic peptide precursor C (NPPC) binds to its receptor, a guanylate cyclase, on cumulus cells to produce cGMP that is transported into the oocyte via gap junctions to maintain meiotic arrest. However, GLYT1 became activated in oocytes within isolated COCs even in the presence of NPPC, indicating that the signaling pathway involved in GLYT1 quiescence is distinct from that which maintains meiotic arrest, even though both normally require the intact follicle and functional gap junctions. (Funding:CIHR)
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".