Aging Is Associated with a Deficiency in Junction-Associated mRNAs in the Testis of the Brown Norway Rat.
Bibliographic record
Abstract
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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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 | 0.001 | 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 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".