UBIQUITIN C-TERMINAL HYDROLASE-ACTIVITY PARTICIPATES IN SPERM ACROSOMAL FUNCTION DURING FERTILIZATION OF PORCINE OOCYTES
Bibliographic record
Abstract
The 26S proteasome, a multi-subunit protease specific for substrateproteins post-translationally modified by ubiquitination, has been implicated in acrosomal function and sperm-zona pellucida (ZP) penetration during mammalian fertilization. Ubiquitin C-terminal hydrolases (UCH) are responsible for the removal of polyubiquitin chains during substrate priming for proteasomal proteolysis. The inhibition of deubiquitination increases the rate of proteasomal proteolysis. Consequently, we have hypothesized that inhibition of sperm acrosome-borne UCHs will increase the rate of sperm-ZP penetration and polyspermy during porcine fertilization in vitro (IVF). Ubiquitin-aldehyde (UA), a specific, nonpermeant UCH-inhibitor, significantly (p<0.05) increased polyspermy during porcine IVF and reduced (p<0.05) UCH-activity measured in motile boar spermatozoa by using a specific fluorometric UCH-substrate, ubiquitin-AMC. Antibodies against two related UCHs, UCH-L1 and UCHL3 detected these UCHs in the sperm acrosome and oocyte cortex, respectively, and increased the rate of polyspermy during IVF, consistent with the UA-induced polyspermy surge. In the oocytes, UCH-L3 was primarily associated with the meiotic spindle. Sperm-borne UCH-L3 was localized to the acrosomal surface and co-immunoprecipitated with a peripheral acrosomal membrane protein, spermadhesin AQN-1. Recombinant UCHs, UCH-L3 and isopeptidase T both reduced polyspermy when added to fertilization medium. UCH-L1 was detected in the oocyte cortex but not on the oocyte or sperm surface, and was partially degraded within 6–8 hours after fertilization. Enucleated oocyte-somatic cell electrofusion caused polarized redistribution of cortical UCH-L1. We conclude that sperm-acrosomal UCHs are involved in sperm-zona interaction and antipolyspermy defense. Modulation of UCH-activity could help managing polyspermy during IVF and provide insight into male infertility. (platform)
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How this classification was reachedexpand
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 | 0.001 |
| 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, 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".