Cholesterol metabolism and Cx43, Cx46, and Cx50 gap junction protein expression and localization in normal and diabetic and obese<i>ob/ob</i>and<i>db/db</i>mouse testes
Bibliographic record
Abstract
Decreased fertility and birth rates arise from metabolic disorders. This study assesses cholesterol metabolism and Cx46, Cx50, and Cx43 expression in interstitium- and seminiferous tubule-enriched fractions of leptin-deficient ( ob/ob) and leptin receptor-deficient ( db/db) mice, two type 2 diabetes and obesity models associated with infertility. Testosterone levels decreased and glucose and free and esterified cholesterol (FC and EC) levels increased in serum, whereas FC and EC levels decreased in the interstitium, in ob/ob and db/db mice. In tubules, a decrease in EC caused FC-to-EC ratios to increase in db/db mice. In tubules, only acyl coenzyme A:cholesterol acyl transferase type 1 and 2 protein levels significantly decreased in ob/ob, but not db/db, mice compared with wild-type mice, and imbalances in the cholesterol transporters Niemann-Pick C1 (NPC1), ATP-binding cassette A1 (ABCA1), scavenger receptor class B member I (SR-BI), and cluster of differentiation 36 (CD36) were observed in ob/ob and db/db mice. In tubules, 14-kDa Cx46 prevailed during development, 48- to 49- and 68- to 71-kDa Cx46 prevailed during adulthood, and total Cx46 changed little. Compared with wild-type mice, 14-kDa Cx46 increased, whereas 48- to 49- and 68- to 71-kDa Cx46 decreased, in tubules, whereas the opposite occurred in the interstitium, in db/db and ob/ob mice. Total and 51-kDa Cx50 increased in db/db and ob/ob interstitium and tubules. Cx43 levels decreased in ob/ob interstitium and tubules, whereas Cx43 decreased in db/db interstitium but increased in db/db tubules. Apoptosis levels measured by ELISA and numbers of apostain-labeled apoptotic cells significantly increased in db/db, but not ob/ob, tubules. Testicular db/db capillaries were Cx50-positive but weakly Cx43-positive with a thickened lamina, suggesting altered permeability. Our findings indicate that the db mutation-induced impairment of meiosis may arise from imbalances in cholesterol metabolism and upregulated Cx43 expression and phosphorylation in tubules.
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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 | 0.001 | 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".