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Testicular Gap (CX43) and Tight Junction (OCLN, CLDN3, 5 and 11) Components in the Dog Are Affected by GnRH-Mediated Downregulation
by
, , , , , and
Sandra Goericke-Pesch
1,2,*
,
Lena Röhrs
1,
Sven Wallrabenstein
1,
Agnete Frimødt Rønnow
3,
Daniela Fietz
4,
Ralph Brehm
5,
Marion Langeheine
5,
Axel Wehrend
1,
Bernd Hoffmann
1,
Hanna Körber
2,† and
Eva-Maria Packeiser
2,† 1
Clinic for Obstetrics, Gynecology and Andrology of Large and Small Animals, Justus-Liebig-University Giessen, Frankfurter Str. 106, 35392 Giessen, Germany
2
Unit for Reproductive Medicine—Clinic for Small Animals, University of Veterinary Medicine Hannover, Foundation, Bünteweg 15, 30559 Hannover, Germany
3
Department of Veterinary Sciences, Section for Veterinary Reproduction and Obstetrics, Faculty of Health and Medical Sciences, University of Copenhagen, Højbakkegård 5, 2630 Tåstrup, Denmark
4
Institute of Veterinary Anatomy, Histology and Embryology, Justus-Liebig-University Giessen, Frankfurter Str. 94, 35392 Giessen, Germany
5
Institute of Anatomy, University of Veterinary Medicine Hannover, Bischofsholer Damm 15, 30173 Hannover, Germany
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Animals 2026, 16(2), 254; https://doi.org/10.3390/ani16020254 (registering DOI)
Submission received: 22 November 2025
/
Revised: 9 January 2026
/
Accepted: 11 January 2026
/
Published: 14 January 2026
(This article belongs to the Special Issue Reproduction in Domestic and Wild Carnivores)
Simple Summary
Slow-release gonadotropin-releasing hormone (GnRH)-agonist implants are used as a medical alternative to surgical castration, reversibly inducing basal testosterone and infertility in male dogs, with full recovery of testicular functions subsequent to implant removal. We hypothesized that the blood–testis barrier, essential for normal spermatogenesis, is reversibly affected by treatment. Gap and tight junction component expressions were studied at mRNA and protein level during efficient treatment and different weeks of recovery following implant removal and compared to untreated adult dogs. In relation to treatment, the blood–testis barrier was disrupted but recovered following recovery of spermatogenesis.
Abstract
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 occludin (OCLN), claudin (CLDN) 3, 5, 11, and connexin (CX) 43 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, OCLN, and CLDN5 expressions). All investigated genes (except CLDN3) differed significantly during restart (W0–12) compared with CG (p < 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.
Keywords:
blood–testis barrier; dog; GnRH-agonist; occludin; claudin; connexin 43
