Spermatozoa lacking TEX51 display hypofertility and defects in morphology
Bibliographic record
Abstract
Fertilization is essential for all sexually reproducing species, yet the complete molecular mechanism remains unclear. Here, we revisit a structure-based search of the AlphaFold human proteome to identify new members of the IST superfamily, a key family of proteins associated with fertilization. We discover that TEX51, predicted to form a 4-helix bundle, a ß-hinge, a pair of CXXC motifs and a transmembrane domain, shares structural similarities with IST superfamily proteins (IZUMO1, SPACA6, and TMEM95). Given the testis-specific expression of TEX51 and conservation across mammals, we hypothesize that TEX51 plays a role in fertilization. To investigate this, we create a Tex51-knockout (KO) mouse model that removes the complete Tex51 open reading frame and incidentally a part of the nearby lncRNA Gm44577. These KO males are hypofertile as shown by in vivo and in vitro analyses, despite showing normal sperm motility. Morphological abnormalities in the KO sperm include disjunction between the flagellum midpiece and principal piece, and an increased presence of cytoplasmic remnants. Electron microscopy further reveals defects in the anchoring of the acrosome to the nucleus. These findings expand the roles of IST superfamily proteins beyond functions in gamete interaction to broader aspects of reproduction such as sperm formation during spermiogenesis.
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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 | 0.000 | 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) | 0.003 | 0.001 |
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".