Vasectomy‐Dependent Dysregulation of a Local Renin‐Angiotensin System in the Epididymis of the Cynomolgus Monkey (<i>Macaca fascicularis</i>)
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Bibliographic record
Abstract
The mammalian epididymis is a fundamental organ for sperm cell maturation; it allows mammals to acquire their fertilizing ability. We have previously shown that during obstruction in cases of vasectomy, gene expression profiles were modified in human and cynomolgus monkey epididymides. Paracrine factors thus appear to be key elements in local gene expression along the epididymis. Local renin-angiotensin systems (RAS) have been described in many other organs as paracrine regulators of gene expression. This work demonstrates the presence of a local RAS in the epididymis of the cynomolgus monkey and investigates the vasectomy-dependent changes occurring in this system. After unilateral vasectomy in 4 monkeys (two for 3 days and two others for 7 days), the presence of two major components of the RAS (ie, angiotensinogen [ANG] and the type 1 receptor to angiotensin II [AT-I]) was evaluated in the vasectomized and the normal controlateral epididymides of each monkey. We also show by in situ hybridization that the principal cells of the epididymis express ANG and AT-I mRNAs and immunohistochemistry permitted to verify the co-localization of the AT-I protein and mRNA. Quantitative comparisons of individual variations in the mRNA and protein profiles for ANG and AT-I revealed that vasectomy altered the RAS expression profiles in an individual manner, thus confirming its role as a local system. This study provides a good basis for further investigation of the possible implications of the RAS in the physiology of the epididymis. Furthermore, the individual dependent modifications are in accordance with the very fluctuating results obtained in the fertility status of human patients undergoing a vasectomy reversal. The variations observed in the RAS expression profiles may be a good model to study the causes of the overall epididymal gene expression dysregulation that follows vasectomy and potentially affects fertility.
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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