Sonic Hedgehog Pathway Inhibition Alters Epididymal Function as Assessed by the Development of Sperm Motility
Why this work is in the frame
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Bibliographic record
Abstract
The sonic hedgehog (Shh) signaling pathway plays a role in pattern orientation in the developing embryo and has been shown to be required for development of the prostate and external genitalia. Recent evidence has shown that important elements of the Shh pathway are also expressed in the adult mouse epididymis at both the gene and protein levels. The objective of the present investigation was to refine the expression pattern of Shh in the mouse epididymis and to determine if the Shh pathway is important for epididymal function vis-à-vis sperm maturation. The former was achieved by microarray analysis of Shh expression in all segments of the mouse epididymis, and the latter was determined by 14-day administration of cyclopamine, a Shh pathway inhibitor, followed by a microassay for the activation and duration of cauda epididymal sperm motility. Shh pathway inhibition was monitored by semiquantitative reverse transcriptase-polymerase chain reaction for expression of epididymal Gli1 and Gli3. The Gli family of transcription factors is commonly activated and regulated by Shh pathway activation. Cyclopamine treatment reduced Gli1 expression by 61% and initiation of cauda sperm motility by 50%. Gli3 expression was reduced by approximately 50%. Subsequent cluster analysis using the microarray data on epididymal gene expression highlighted several potential target genes for the Shh pathway, the most prominent of which is prostaglandin D2 synthase. These results indicate that an operating Shh pathway is important in the murine epididymis for the development of sperm motility and implies a role for Shh signaling in adult epididymal function.
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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 | 0.001 | 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 it