Testicular Gap (CX43) and Tight Junction (OCLN, CLDN3, 5 and 11) Components in the Dog Are Affected by GnRH-Mediated Downregulation

Following the downregulation of testicular endocrine and germinative function by slow-release gonadotropin-releasing hormone (GnRH)-agonist implants, testicular functions are quickly restored after implant removal. As an intact blood-testis barrier (BTB) is crucial for normal spermatogenesis and its integrity is FSH- and androgen-dependent, alterations in the BTB gene and protein expressions during downregulation and subsequent restart seem inevitable. We investigated <i>occludin</i> (<i>OCLN</i>), <i>claudin</i> (<i>CLDN</i>) <i>3</i>, <i>5</i>, <i>11,</i> and <i>connexin</i> (<i>CX</i>) <i>43</i> mRNA-, and CLDN11 and CX43 protein expressions during GnRH implant-induced downregulation (W0) and restart of spermatogenesis after implant removal (week, W, 3-12). Untreated juvenile (JG) and adult dogs (CG) served as controls. Sertoli cells were significantly affected by treatment (reduced nuclear area, <i>OCLN</i>, and <i>CLDN5</i> expressions). All investigated genes (except <i>CLDN3</i>) differed significantly during restart (W0-12) compared with CG (<i>p</i> < 0.05). CLDN11 and CX43 immunopositive staining was absent or diffuse cytoplasmic at downregulation and relocated at W9, indicating disruption and subsequent restorage of BTB. As W0 and JG differed considerably, our results suggest that the model cannot mimic puberty. In conclusion, GnRH implant-induced long-term gonadotropin suppression disrupts testicular CX43 and CLDN11 distribution and changes gap and tight junction mRNA expression. Treatment effects are reversible suggesting re-establishment of the BTB.