3 Modulation of glycolysis alters histone acetylation and gene expression in bovine blastocysts produced in vitro
Notice bibliographique
Résumé
Changes in the dynamics of energy metabolism can affect the sophisticated molecular control of different cell types including embryonic stem cells (Zhang et al. 2018 Cell Metab. 27, 332-338; https://doi.org/10.1016/j.cmet.2018.01.008). In this study, we modulated pathways related to acetyl-CoA generation, the major donor for histone acetylation, and explored how this affects histone acetylation and the transcriptional profile of bovine blastocysts. Embryos were produced in vitro by conventional protocols. On Day 4 of culture (Fertilization = Day 0), embryos were randomly allocated into 3 experimental groups according to culture medium [synthetic oviductal fluid with amino acids (SOFaa) + 4% bovine serum albumin] supplementation: Control (no additional supplementation), sodium iodoacetate (IA; 2 µM; glycolysis inhibitor), and sodium dichloroacetate (DCA; 2 mM; acetyl-CoA conversion stimulator). Expanded blastocysts were collected on Day 7 and assessed for ATP levels (luminescence), mitochondrial activity (MitoTracker Red CMXRos; ThermoFisher Scientific), histone 3 lysine 9 and 27 acetylation (H3K9ac and H3K27ac; immunostaining) and transcriptional profiling by RNA sequencing (RNA-Seq) of isolated inner cell mass. Data were submitted to normality test and treatment groups were compared to control using t-test or Mann–Whitney test for non-parametric data (mean ± s.e.) considering P < 0.05. RNA-Seq data were analysed by DESEqn 2 and transcripts with Padj <0.05 were submitted to gene ontology by DAVID (https://david.ncifcrf.gov/). Mitochondrial activity was higher in DCA compared with Control (control: 53078 ± 2747 AU vs. DCA: 57520 ± 902 AU; P = 0.0034), which explains the higher ATP levels found in this group (control: 1.49 ± 0.65 µM vs. DCA: 41.56 ± 15.69 µM; P = 0.03). However, although mitochondrial activity was expectedly lower in IA compared to control (control: 53078 ± 2747 A.U. vs. DCA: 36249 ± 3200 A.U.; P = 0.0013), we did not observe a decrease in ATP levels (control: 1.49 ± 0.65 µM vs. IA: 3.23 ± 1.13 µM; P = 0.12). Confirming our hypothesis, modulation of acetyl-CoA generation affected histone acetylation, with levels of H3K9ac and H3K27ac being higher in DCA and lower in IA compared with Control (H3K9ac Control: 988.3 ± 22.82 AU, DCA: 1301 ± 32.28 AU, IA: 684 ± 23.7 AU; P < 0.0001 and H3K27ac Control: 502.5 ± 13.64 AU, DCA: 667.2 ± 12.19 AU, IA: 417.2 ± 12.03 AU; P < 0.0001). Finally, 905 genes were differentially expressed, 599 up- and 306 downregulated in DCA compared with Control. Another 675 genes were differentially expressed between control and IA, (385 up- and 290 downregulated in IA). Gene ontology indicated that, compared with control, the biological functions upregulated in DCA were related to developmental process and the downregulated functions were associated with metabolism regulation, indicating a role of metabolic pathways in the developmental competence of the embryo. IA, in contrast, had catabolic activity upregulated and nucleotide metabolism downregulated compared with control, supporting the depletion of metabolic activity and lower acetylation. Taken together, our results demonstrate that the modulation of energy metabolism affects the epigenetic status of bovine embryos with consequences for the transcriptional profile of pathways involved in embryo quality and viability.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».