CHANGES IN THE AMOUNTS OF MITOCHONDRIAL DESOXYRIBONUCLEIC ACID DELETIONS AND TRANSCRIPTS IN OOCYTES FROM AGED MICE
Bibliographic record
Abstract
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)
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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 | 0.001 | 0.001 |
| 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".