89 Embryonic metabolism orchestrates epigenetic mechanisms: What can we anticipate from the first cleavages?
Bibliographic record
Abstract
Intermediates of the energy metabolism (as acetyl Co-A) can donate their acetyl group to introduce acetylation in histones, establishing a relationship between metabolism and epigenetic control in somatic and embryonic stem cells. Embryos with different kinetics during the first cleavages also have alterations in epigenetic profile as well as in metabolism and energy substrate consumption during in vitro culture. The aim of this work was to verify if and how this relation between metabolism and epigenetic parameters was also presented in in vitro-produced bovine embryos. For that, we first characterised the pattern of H3K9ac, and the molecular pattern of enzymes involved with histone acetylation and acetyl-CoA production in female blastocysts derived from fast and slow cleavage embryos. To validate the results, we also produced bovine embryos cultured with an inhibitor of the pyruvate production, and consequently the acetyl Co-A generation to check if this could interfere in the H3K9ac pattern. For this, embryos were in vitro produced following standard protocol and classified at 40 hours post-insemination as fast (4 or more cells) or slow (2 cells) and collected at the blastocyst stage. Blastocysts were immunostained to H3K9ac and the fluorescence intensity of each nucleus was quantified using ImageJ and analysed by Student's t-test. For transcript quantitation, RNAseq data were accessed from a previous report using the same kinetics classification model (Milazzotto et al. 2016 Mol. Rep. Dev. 83, 324-336; https://doi.org/10.1002/mrd.22619) and analysed using limma-voom on Galaxy 3.38.3. To validate the results, bovine embryos were produced and cultured until Day 4 and then incubated until the blastocyst stage with different doses of iodoacetate (IA; 2 and 5 mM) to reduce the intracellular levels of acetyl CoA. These blastocysts were also assessed by H3K9 acetylation. Slow blastocysts presented higher fluorescence intensity for H3K9ac than fast blastocysts (fast 13.33 ± 0.37 AU vs. slow 38.14 ± 1.17 AU; P < 0.0001). Despite the fact that there were no differences in transcripts related to this acetylation (ELP3 and HAT2), slow blastocysts presented higher levels of transcripts for PDHB1 and PDHA1, responsible for acetyl-CoA production (PDHB1: fast 11.6 ± 0.2CPM vs. slow 13.1 ± 0.2 counts per million; P < 0.01 PDHA1: fast 12.6 ± 0.2 CPM vs. slow 13.2 ± 0.3 CPM; P < 0.01). The reduction of acetyl-CoA in blastocysts induced by IA led to lower levels of H3K9ac in 1 and 2 mM doses when compared with the control (control: 43.8 ± 0.7 AU; 1 mM: 34.7 ± 0.5 AU; 2 mM: 30.1 ± 0.6 AU; P < 0.0001). Interestingly, H3K9ac levels were similar for 5 mM IA and control group (5 mM: 41.2 ± 1.4; P > 0.05), suggesting a compensatory mechanism in extreme cases to maintain the histone acetylation. As far as we know, this is the first work that describes a relation between metabolism and epigenetics in bovine embryos. Although the pattern of genes related to acetylation seems to be unaltered, changes in acetyl Co-A production pathway exert an influence on H3K9ac status. Grant support was provided by grant 2017/18384-0 and 2018/11668-6 from FAPESP and CAPES.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.000 |
| 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".