Aging Is Associated with a Deficiency in Junction-Associated mRNAs in the Testis of the Brown Norway Rat.
Notice bibliographique
Résumé
Germ cell differentiation in the seminiferous epithelium is facilitated by the dynamic associations between the germ cells and the Sertoli cells. These cell adhesions or junctions not only tether the cells of the seminiferous epithelium together but also assist in the movement of germ cells across the blood seminiferous tubule barrier (BSTB). The BSTB is situated between the pre- and post-meiotic germ cells (i.e. the pre-leptotene and pachytene spermatocytes); it prevents exposure of the post-meiotic germ cells to harmful chemicals that may be present in the systemic circulation and protects the spermatids, which express "foreign" proteins, from immunological attack. There are decreases in fertility with increasing age in both men and animal models. The Brown Norway rat has been established as an excellent model for male reproductive aging as it shows many characteristics similar to those of aging men. We hypothesize that as male rats age the proteins involved in forming the junctions within the testis decrease and that this will affect the ability of the BSTB to protect post-meiotic germ cells. To test this hypothesis, we used Brown Norway rats at 4 months of age (young) and 18 months (aged). At 18 months of age the seminiferous epithelium still has a full complement of germ cells; testicular atrophy does not occur until around 20 months. Pachytene spermatocytes were isolated from testes using the STA-PUT velocity sedimentation technique, achieving at least 83% purity. RNA was extracted from this cell population and gene expression was assessed using Affymetrix rat 230 2.0 whole rat genome microarrays. Raw data were analysed using Genespring v10 (Agilent Technologies) and Pathway Studio. Microarray data were confirmed by q-RT-PCR and protein expression was analysed using Western blotting. Of the 1200 probe sets that were significantly decreased in the microarray by at least 1.5 fold, more than 50 (4%) were involved in cell adhesion; of these, 20 (2%) are known to be specifically involved in junction dynamics within the seminiferous epithelium. Jam2, Ocln, cdh2 (N-cadherin), ctnnb (β-catenin), ctnna (α-catenin), lama and cldn11 (involved in adherens and tight junctions), among others, were each decreased by approximately 50% in aged spermatocytes. In addition, Rac1, cdc42, Rap1a and Rap1b, GTPases involved in the recruitment of cadherins to the adherens junctions found between Sertoli and germ cells, were similarly decreased in aged spermatocytes. Thus, there is a decrease in the expression of the transcripts for cell adhesion molecules with increasing age. Preliminary data indicate similar decreases in the respective proteins that are involved in maintaining junction integrity within the testis. We propose that decreased expression of these gene products may lead to a collapse of the BSTB, providing the opportunity for harmful substances and/or immune cells to cross the BSTB and cause the disruption of spermatogenesis that is observed in this model with increasing age. This work was supported by a grant from CIHR. (platform)
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Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| 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 | 0,001 | 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) | 0,001 | 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 source (Gemma direct ou Codex distillé), 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 ».