Modified cytoskeletal and extracellular matrix composition in the canine testis after long-acting gonadotropin-releasing hormone agonist deslorelin treatment.

BACKGROUND: Long-acting gonadotropin-releasing hormone (GnRH) agonists are commonly used for fertility control in male dogs. Their effect on testicular histomorphology has not been clarified. OBJECTIVES: To elucidate the mechanisms underlying androgen withdrawal in response to long-acting GnRH agonist deslorelin 4.7 mg treatment on testicular histomorphology and key extracellular matrix (ECM) and cytoskeletal components. MATERIALS AND METHODS: Testes of deslorelin-treated dogs (n = 5) were evaluated at maximum downregulation of germinative and steroidogenic function, and compared with untreated (control) adult (n = 7) and prepubertal immature (n = 8) dogs. Morphological analysis was performed with Crossman's triple staining and periodic-acid-Schiff (PAS). Localization of smooth muscle α-actin (αSMA/ACTA2), desmin (DES), elastin (ELN), collagen type I (COL1A1), collagen type IV (COL4A1) was detected by immunohistochemistry. RESULTS: Deslorelin treatment resulted in complete absence of germ cells except for spermatogonia. Crossman's triple staining identified thickening of peritubular connective tissue characterized by small infoldings toward the lumen of atrophied seminiferous tubules, and the expansion of interstitial area. PAS staining revealed a thickened basement membrane and phagosome-like particles within the seminiferous tubules. In control dogs, αSMA/ACTA2, DES, ELN, COL1A1, and COL4A1 were localized to blood vessels and the peritubular wall of seminiferous tubules. ELN, COL1A1, and COL4A1 were also found in stromal compartments. A similar localization pattern with signals within a thickened peritubular area was found in deslorelin-treated dogs. Prepubertal dogs had similar distribution but weaker signal intensity in the peritubular wall of seminiferous tubules. Positive area percentages of αSMA/ACTA2, DES, ELN, and COL4A1 were the highest in deslorelin-treated dogs, while COL1A1 was the lowest in control, intermediate in deslorelin-treated, and highest in prepubertal dogs. CONCLUSION: Deslorelin treatment caused infertility with accumulation of collagen (COL4A1, COL1A1) and deposition of αSMA/ACTA2, DES, and ELN within the thickened lamina propria surrounding seminiferous tubules. Peritubular myocytes maintained their smooth muscle phenotype despite androgen withdrawal. The immature testis had lower abundance of most cytoskeletal and ECM proteins.