Regulation of porcupine-dependent Wnt signaling is essential for uterine development and function
Bibliographic record
Abstract
Abstract Six members of the Wnt family are expressed in the female reproductive tract. Their collective function ensures proper development of the uterus, preparing it for pregnancy during adulthood. Here, we take advantage of the fact that Porcn, a prerequisite for all Wnt secretion, is located on the X chromosome, to generate females that were mosaic for Porcn throughout the reproductive tract. Porcnflox/+ females were mated with progesterone receptor (Pgr)-Cre males (PgrCre/+) to generate females that were heterozygous for Porcupine in all tissues of the female reproductive tract, resulting in mosaicism due to random X-inactivation. We demonstrated that Porcn mosaic females are extremely subfertile and exhibit a large spectrum of phenotypes ranging from morphologically normal uteri to uteri with extremely enlarged cystic glands. Decreased fertility in Porcupine mosaic females was not associated with phenotype severity and was observed regardless of whether or not cystic glands were enlarged. By crossing-in a GFP reporter on the wild-type X chromosome, we were able to correlate endometrial gland hyperplasia with a mostly Porcupine mutant stroma, demonstrating the role of stromal Wnts in the regulation of endometrial gland proliferation. Finally, we demonstrated that fertility issues within mosaic females were due to a reduced response to estrogen and to abnormal Tcf/Lef signaling across the mesometrial-anti-mesometrial axis during the window of implantation.
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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".