Stimulation or Inhibition of AMPK Causes Arrest of Mouse Embryo Development.
Bibliographic record
Abstract
AMPK (AMP-regulated kinase) is a kinase involved in nutrient- and stress-sensing. In general, its role is to conserve ATP by shutting down anabolic pathways and increasing activity of transport and catabolic pathways. AMPK is known to be dysregulated in diabetes and obesity and is a target of some diabetic drugs such as metformin. There is a role for AMPK in mammalian oocyte maturation, however, little is known of its role in later embryo development. Two-cell mouse embryos were cultured in KSOM under 5% oxygen conditions in the presence of increasing concentrations of AICAR, an AMPK activator, or Compound C, an AMPK inhibitor. Blastocyst development was evaluated at 48h of culture. Embryo diameters were measured, and embryos fixed for immunofluorescent staining. Concentrations of AICAR above 250 micromolar, decreased blastocyst development and embryo diameter (250: 10.9 ± 3.3% and 76.29 ± 1.86 microns and 1000: 1.0 ± 1.0% and 71.27 ± 0.65 microns vs. 0: 44.6 ± 10.8% and 108.18 ± 2.69 microns, P < 0.05). Diameter was also decreased at with the 100 micromolar dose of AICAR, 84.54 ± 2.45 microns, P < 0.05. Most embryos seemed to arrest at the morula stage. Similarly, Compound C at 100 micromolar decreased blastocyst development to 9.2 ± 5.5% and 85.82 ± 1.56 microns compared to the DMSO control at 39.5 ± 14.9% and 114.50 ± 2.34 microns, P < 0.05. Using confocal microscopy, embryos that were arrested by AICAR treatment appeared to have lower immunofluorescence for ZO-1, a tight junction protein, in the membrane and possibly lower expression of actin. Interestingly, the active phosphorylated AMPK protein appeared to be expressed mostly in the cytoplasm in the inner cell mass, and in the nucleus, perinuclear area and in the membrane of trophectoderm cells. Membrane staining has only been observed in a few cell types. AMPK activation may need to be regulated within a narrow window to ensure proper embryo development. Research supported by NSERC to A.J.W. (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 | 0.000 | 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".