Alpha-ketoglutarate modulates the reprogramming of mitochondrial and nuclear DNA methylation during the earliest stages of the bovine preimplantation embryo development
Bibliographic record
Abstract
During the preimplantation embryonic development, metabolic and epigenomic remodeling are crucial events that can be significantly impacted even by minor environmental changes. Right after fertilization, nuclear deoxyribonucleic acid (DNA) undergoes demethylation, reaching the lowest levels at the 8-16 cell stage, marking the onset of mitochondrial metabolism and genome activation. This coincides with "de novo" DNA methylation events guiding cell lineage differentiation at the blastocyst stage. High levels of α-ketoglutarate (AKG) in cancer and pluripotent stem cells promote a more undifferentiated state, acting as a cofactor for ten-eleven translocation (TET) demethylases. In this study, we examined the metaboloepigenetic adaptations from AKG supplementation during the in vitro culture in a bovine model. Bovine embryos were produced in vitro and culture until Day 4 in the presence or not of 4 mM of AKG. After AKG discontinuation, embryos remained in culture until Day 7 for blastocyst analysis. AKG during the early stages of development led to the expected increase in the levels of TET family enzymes, resulting in a decrease in nuclear 5mC levels. Additionally, the blastocysts derived from the AKG group exhibited reduced mitochondrial activity in the inner cell mass, along with increased methylation levels of mitochondrial DNA. Integrative analysis of DNA methylation and transcription revealed low correlation between these two omics, with a higher effect of AKG treatment on DNA methylation than the ribonucleic acid content. These results indicate that minor metabolic alterations early in development, such as AKG supplementation, have a significant impact on the embryo's metabolism and molecular control, compromising the epigenetic reprogramming.
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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".