P-801 Human umbilical cord perivascular cells (HUCPVC) reduce ovarian fibrosis and improve pregnancy rates in a mouse model of natural ovarian aging
Bibliographic record
Abstract
Abstract Study question Does repeated intravenous administration of human umbilical cord perivascular cells (HUCPVC) during the period of ovarian aging prevent age-related fertility decline in a mouse model? Summary answer Repeated administration of first trimester and term HUCPVC improved pregnancy rates and reduced ovarian fibrosis in a mouse model of natural ovarian aging. What is known already Mesenchymal stromal cells (MSC), such as first trimester (FTM) and term human umbilical cord perivascular cells (HUCPVC), may be good cell candidates to mitigate side-effects of oncotherapy, including infertility, and are also gaining interest in ovarian rejuvenation strategies. The intraovarian or systemic administration of various sources of mesenchymal stromal cells in animal models of advanced reproductive age have been previously reported to improve ovarian reserve, follicle activation and function, via multiple proposed mechanisms. However, mating studies have not previously been performed to demonstrate fertility preservation. In addition, the optimal dose regimen and timing of treatment has not been established. Study design, size, duration Pre-clinical randomized controlled study in a mouse model of natural ovarian aging from 6 months to 12 months, including a negative control group (vehicle-treated), a cell control group (fibroblast-treated) and 3 experimental groups (HUCPVC, 2 sources and 2 dose regimens; n = 10-15 per group). All parameters were compared with young control female mice (6-8 weeks, 6 months). Cell injections and all assessments were blinded. Participants/materials, setting, methods 6-month-old ICR mice randomized into 4 groups received 6 monthly tail vein injections of 1x106 HUCPVC (FTM or term), fibroblast cells or HBSS (vehicle control). A 5th group received a single injection of FTM HUCPVC at 11M (n = 5). Pregnancy and litter size data were collected after breeding trials. The total number of follicles per ovary and picrosirius red (PSR) staining were quantified. Serum anti-Mullerian hormone (AMH) and C-reactive protein (CRP) were analyzed by ELISA. Main results and the role of chance No differences in mortality rates (P = 0.2) and animal weights were observed. The weight gain in FTM and term HUCPVC treated animals was significantly greater than in the other groups, over the duration of the study (P = 0.04). Animals that received 6 injections of FTM and term HUCPVC showed significantly higher pregnancy rates at 12M (100%, 80%) (P = 0.007; P = 0.048, respectively), when compared to animals that received HBSS (40%) and were similar to pregnancy rates of 6-8weeks (100%) and 6M (77%) groups. Fibroblast-treated and 1x FTM HUCPVC-treated groups showed 60% pregnancy rates. Age-associated declines in litter sizes and ovarian reserve indicators were observed as expected, but not rescued by cell treatments, except for levels of AMH which were increased in the group that received 1x FTM HUCPVC injections when compared to HBSS controls (P = 0.04). Age-associated increases in ovarian stroma fibrosis were observed with aging in the control groups (P < 0.0001), and were significantly reduced in 6x FTM HUPCVC, 6x term HUCPVC and 1x FTM HUCPVC groups, when compared to HBSS and fibroblast controls (P < 0.0001; P = 0.01 and P < 0.0001, respectively). An age-associated increase in CRP (P = 0.01) was significantly decreased in 6x FTM HUCPVC-treated groups, when compared to HBSS (P = 0.04). Limitations, reasons for caution Pregnancy rate (the main outcome measured in this study) may confound some of the secondary outcomes analyzed (CRP levels). Use of ovarian tissue for histological analysis and limited serum samples precluded further molecular analyses to assess potential mechanisms for the effects of HUCPVC. Wider implications of the findings FTM HUCPVC have anti-inflammatory and anti-fibrotic effects, and represent a promising source of MSC to prevent fertility decline in women of advanced reproductive age. Trial registration number Not Applicable
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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 | 0.000 |
| 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".