In vitro inhibition of rat cauda epididymal sperm glycolytic enzymes by ornidazole, α‐chlorohydrin and 1‐chloro‐3‐hydroxypropanone
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Bibliographic record
Abstract
Chlorinated antifertility compounds are known to inhibit glycolysis of spermatozoa as they reside in the epididymis but new compounds need to be evaluated that retain antifertility action but do not exhibit side-effects. In this study, two known antifertility agents and a related compound were compared for their inhibition of rat sperm metabolism and motility in vitro. The dose-dependent inhibition in vitro of the glycolytic enzymes glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and triosephosphate isomerase (TPI) of distal cauda epididymal rat spermatozoa by (R)-, (S)- and (R,S)-ornidazole (ORN), (R,S)-alpha-chlorohydrin (ACH) and 1-chloro-3-hydroxypropanone (CHOP) was compared. The direct inhibition of GAPDH by ORN suggests that it inhibits without prior conversion outside the cell but inhibition was not stereo-specific. The GAPDH, but not TPI, activity of spermatozoa incubated with ACH and CHOP was highly correlated with kinematic parameters of spermatozoa incubated in pyruvate- and lactate-free medium. ACH only inhibited the activity of intact spermatozoa and the inhibition was not reversed by washing the particulate sperm fraction after sonication. High concentrations of ACH (100 mmol/L) killed intact rat spermatozoa and decreased the extent of GAPDH inhibition. CHOP, unlike ACH, was an effective inhibitor of both intact and sonicated cells. Pre-CHOP, the dimethylketal precursor of CHOP, and its other hydrolysis product MeOH, were both ineffective in vitro. CHOP and related ketals may be more effective inhibitors of sperm glycolysis than ACH and may prove useful for investigating sperm-specific glycolytic inhibition, a prerequisite for the development of antiglycolytic, post-testicular acting contraceptives.
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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 | 0.000 | 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 it