N-cadherin mechanosensing in ovarian follicles controls oocyte maturation and ovulation
Bibliographic record
Abstract
ABSTRACT The cell adhesion molecule N-cadherin (CDH2) is a membrane component of adherens junctions which regulates tissue morphogenesis and architecture. In the follicles of mammalian ovaries, N-cadherin adherens junctions are present between granulosa cells, cumulus cells and at the interface of cumulus cell transzonal projections and the oocyte. We demonstrate a mechanosensory role of N-cadherin integrating tissue structure and hormonal regulation of follicular morphogenic events including expansion of the cumulus oocyte complex (COC) matrix, oocyte maturation and ovulation. Two small molecule N-cadherin antagonists inhibited COC maturation in vitro . Transcriptome profiling revealed that targets of β-catenin and YAP1 pathways were dysregulated by N-cadherin antagonists. In vivo , N-cadherin antagonist significantly reduced ovulation in mice compared to controls (11 vs 26 oocytes/ovary; p=5.8×10 -6 ). Ovarian follicles exhibited structural dysgenesis with granulosa and cumulus cell layers becoming disorganised and the connection between cumulus cells and the oocyte disrupted and the transcriptome again indicated altered mechanical sensing causing dysregulation of the Hippo/YAP and β-catenin pathways and ECM reorganization. Granulosa specific N-cadherin depletion in Cdh2 Fl/FL ;Amhr2-Cre also showed significantly altered mechanosensitive gene expression and reduced ovulation. Our findings demonstrate a critical role for N-cadherin in ovarian follicular development and ovulation, and the potential to inhibit ovulation through targeting this signalling mechanism.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 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) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".