Impaired function of the blood-testis barrier during aging is preceded by a decline in cell adhesion proteins and GTPases.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science

Aging/*physiology ; Blood-Testis Barrier/*physiopathology ; Cell Adhesion Molecules/*metabolism ; GTP Phosphohydrolases/*metabolism ; Gene Expression Regulation/*physiology; Animals ; Blotting, Western ; Fluorescein-5-isothiocyanate ; Gene Expression Profiling ; Germ Cells/pathology ; Male ; Microarray Analysis ; Rats ; Real-Time Polymerase Chain Reaction ; Spermatocytes/chemistry ; Spermatogenesis/physiology

With increasing age comes many changes in the testis, including germ cell loss. Cell junctions in the testis tether both seminiferous epithelial and germ cells together and assist in the formation of the blood-testis barrier (BTB), which limits transport of biomolecules, ions and electrolytes from the basal to the adluminal compartment and protects post-meiotic germ cells. We hypothesize that as male rats age the proteins involved in forming the junctions decrease and that this alters the ability of the BTB to protect the germ cells. Pachytene spermatocytes were isolated from Brown Norway rat testes at 4 (young) and 18 (aged) months of age using STA-PUT velocity sedimentation technique. RNA was extracted and gene expression was assessed using Affymetrix rat 230 2.0 whole rat genome microarrays. Microarray data were confirmed by q-RT-PCR and protein expression by Western blotting. Of the genes that were significantly decreased by at least 1.5 fold, 70 were involved in cell adhesion; of these, at least 20 are known to be specifically involved in junction dynamics within the seminiferous epithelium. The mRNA and protein levels of Jam2, Ocln, cdh2 (N-cadherin), ctnna (α-catenin), and cldn11 (involved in adherens junctions), among others, were decreased by approximately 50% in aged spermatocytes. In addition, the GTPases Rac1 and cdc42, involved in the recruitment of cadherins to the adherens junctions, were similarly decreased. It is therefore not surprising that with lower expression of these proteins that the BTB becomes diminished with age. We saw, using a FITC tracer, a gradual collapse of the BTB between 18 and 24 months. This provides the opportunity for harmful substances and immune cells to cross the BTB and cause the disruption of spermatogenesis that is observed with increasing age.

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MOP-89767 Canada Canadian Institutes of Health Research

0 (Cell Adhesion Molecules)
EC 3.6.1.- (GTP Phosphohydrolases)
I223NX31W9 (Fluorescein-5-isothiocyanate)

Date Created: 20140107 Date Completed: 20140902 Latest Revision: 20211021

20221213

PMC3877286

10.1371/journal.pone.0084354

24391944