PABP Interacting Protein 2 (Paip2) Is a Major Translational Regulator Involved in the Maturation of Male Germ Cells and Male Fertility.
Notice bibliographique
Résumé
Paip2 regulates translation by promoting the dissociation of PABP (PolyA Binding Protein) from the poly(A)tails of mRNA. There are 2 homologs of Paip2,Paip2A and Paip2B, that are highly expressed in the pancreas. In the testis, Paip2A is highly expressed whereas Paip2B levels are low. During spermatogenesis, mRNAs are stored in the male germ cells as transcription is active until early spermiogenesis in round spermatids. Translation is tightly regulated during spermiogenesis since, in the absence of any transcriptional activity, several proteins are only expressed at very specific steps. Some mechanisms by which translation is regulated during the late phase of spermatogenesis have been suggested but this remains unclear. Using immunohistochemistry, we have shown that Paip2A and PABP are both specifically expressed in the testicular germ cells showing an overlapping expression during spermiogenesis. Paip2A is expressed in spermatids from steps 7-8 of spermiogenesis until the sperm are released. PABP starts to be expressed in the pachytene spermatocytes at stages 5 and its expression increases gradually in the round spermatids, to finally disappear in the elongating spermatids at step 15 of spermiogenesis. In order to understand the role of Paip2 in spermatogenesis and male fertility, we characterized a double knock-out (DKO) transgenic mouse lineage in which both Paip2A and Pai2B genes were inactivated. By continuous mating with wild type (wt) partners, we showed that DKO females presented normal fertility whereas DKO male mice were infertile. When compared to wt males, the DKO males had a 6% lower body weight as well as significantly lower epididymal (25% less) and prostatic weights (71% less). No spermatozoa could be found in the cauda epididymidis and the testis sperm head count was significantly decreased by 64%. Histological examination of the testes revealed abnormalities with vacuolization in some tubules and abnormal alignment of the spermatozoa at the lumen at stages 7-8, thus suggesting that the elongated spermatids in the DKO mouse are retained and cannot be released into the lumen properly. Moreover, we have shown an abnormal expression of PABP in the single Paip2A knock-out male germ cells where PABP is still expressed in elongated spermatids at stage 8 and staining can be found in the lumen all along the epididymis. We hypothesize that Paip2 translation factors are major players in the development of male germ cells, regulating the translation of key proteins involved in chromatin condensation and sperm release during spermiogenesis. Supported by CIHR. (platform)
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».