CHANGES IN THE AMOUNTS OF MITOCHONDRIAL DESOXYRIBONUCLEIC ACID DELETIONS AND TRANSCRIPTS IN OOCYTES FROM AGED MICE
Notice bibliographique
Résumé
Aging is a multifactorial phenomenon characterized by a decline of the physiological function in general, which can be explained by a diminished mitochondrial respiratory function due to oxidative damage to the mitochondrial (mt) DNA. In fact, mtDNA damage is characterized by an accumulation of point mutations and rearrangements (especially deletions) in most tissues at a rate much faster than for the nuclear genome. Although a large number of mtDNA deletions have been reported, ranging from 6 to 10, 422 bp in size, the most common deletion has a length 4977 bp in human beings and 4974 bp in mice. Moreover, the presence of this common deletion has been correlated with age in a variety of somatic tissues, and some studies have identified the common deletion in oocytes and, to a lesser extent, in early stage embryos. There is also a significant increase in the frequency of deleted mtDNA in oocytes that remain unfertilized or arrested after in vitro fertilization, leading to lower expression levels of ATPase6, CO III, and ND3 genes. The objectives of this project were to better characterize the alterations in mtDNA from mature germinal vesicle (GV) stage oocytes during the process of ageing and to correlate these alterations with changes in fertility. C57BL/6 females between 2 and 24 months were divided into age groups and caged for up to 3 months with fertile C57BL/6 males to determine fertile status. Each female was primed with 5 IU of PMSG and 48 h after 5 IU of hCG, and sacrificed 90 minutes after hCG injection. Cumulusoocyte-complexes were collected from the ovaries, denuded of cumulus and frozen for later analysis. Genomic DNA was extracted to measure the copies of total mtDNA and mtDNA common deletion using, real time PCR. Messenger RNA was recovered to measure transcripts abundance of nuclear- (NDUFS4) and mitochondrial- (ND2 and ND4) encoded genes, which were measured using quantitative RT-PCR. During ageing, we found that GV oocytes showed a decrease in mtDNA copy number and an increase in the proportion of mtDNA carrying the common deletion. Whereas no consistent changes in NDUFS4 were observed, GV oocytes from old females showed a significant reduction in transcripts for the mitochondrial encoded ND4 and a trend for fewer transcripts of the ND2 gene. In the case of fertility, we observed more mtDNA copies in GV from fertile than infertile females. There was also a trend of a higher percentage of mtDNA with the common deletion in the infertile group. There were no differences between the groups in the transcripts of NDUFS4, ND2 or ND4. These results indicate that the process of ageing affects the quantity (copy number) and quality (% deleted) mtDNA of GV oocytes, and seem to lower their ability to generate mtDNA encoded transcripts. Since similar mtDNA anomalies were also observed in GV oocytes derived from females unable to produce offspring, these data suggest a relationship between mtDNA functionality and age-related infertility. (platform)
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 machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 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 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,001 |
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 source (Gemma direct ou Codex distillé), 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 ».