WD-repeat containing protein-61 regulates endometrial epithelial cell adhesion indicating an important role in receptivity
Why this work is in the frame
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Bibliographic record
Abstract
Endometrial receptivity is crucial for successful embryo implantation during early pregnancy. The human endometrium undergoes remodeling within each menstrual cycle to prepare or become receptive to an implanting blastocyst in the mid-secretory phase. However, the mechanisms behind these changes are not fully understood. Recently, using hormone-treated endometrial organoids to model receptivity, we identified that the transcriptional regulator WD-repeat-containing protein-61 (WDR61) was reduced in organoids derived from infertile women. In this study, we aimed to determine the role of WDR61 in endometrial receptivity. Here, we demonstrated that WDR61 immunolocalizes in the nuclei and cytosol of endometrial glandular epithelium, luminal epithelium, and stroma. The staining intensity of WDR61 was significantly higher during the receptive mid-secretory phase compared to the non-receptive proliferative phase in fertile women. In a functional experiment to model blastocyst adhesion to the endometrial epithelium, we found that adhesion of cytotrophoblast progenitor spheroids was blocked when siRNA was used to knockdown WDR61 in primary endometrial epithelial cells. Similarly, in Ishikawa cells (a receptive human endometrial epithelial cell line), siRNA knockdown of WDR61 significantly reduced the cell adhesive and proliferative capacities. qPCR revealed that WDR61 knockdown reduced expression of key genes involved in receptivity including HOXD10, MMP2, and CD44. Chromatin immunoprecipitation sequencing demonstrated that WDR61 directly targeted 2022 genes in Ishikawa cells, with functions including focal adhesion, intracellular signaling and epithelial-mesenchymal transition. Overall, these findings suggest that WDR61 promotes endometrial receptivity by modulating epithelial cell focal adhesions, proliferation, and epithelial-mesenchymal transition.
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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 | 0.002 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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 it