Angiotensin-converting enzyme inhibitors of Bothrops jararaca snake venom affect the structure of mice seminiferous epithelium

Abstract

BackgroundConsidering the similarity between the testis-specific isoform of angiotensin-converting enzyme and the C-terminal catalytic domain of somatic ACE as well as the structural and functional variability of its natural inhibitors, known as bradykinin-potentiating peptides (BPPs), the effects of different synthetic peptides, BPP-10c (<ENWPHQIPP), BPP-11e (<EARPPHPPIPP), BPP-AP (<EARPPHPPIPPAP) and captopril were evaluated in the seminiferous epithelium of male mice.MethodsThe adult animals received either one of the synthetic peptides or captopril (120 nmol/dose per testis) via injection into the testicular parenchyma. After seven days, the mice were sacrificed, and the testes were collected for histopathological evaluation.ResultsBPP-10c and BPP-AP showed an intense disruption of the epithelium, presence of atypical multinucleated cells in the lumen and high degree of seminiferous tubule degeneration, especially in BPP-AP-treated animals. In addition, both synthetic peptides led to a significant reduction in the number of spermatocytes and round spermatids in stages I, V and VII/VIII of the seminiferous cycle, thickness of the seminiferous epithelium and diameter of the seminiferous tubule lumen. Interestingly, no morphological or morphometric alterations were observed in animals treated with captopril or BPP-11e.ConclusionsThe major finding of the present study was that the demonstrated effects of BPP-10c and BPP-AP on the seminiferous epithelium are dependent on their primary structure and cannot be extrapolated to other BPPs.

Toxicological effects of bioactive peptide fractions obtained from Bothrops jararaca snake venom on the structure and function of mouse seminiferous epithelium

“…BPP-10c and BPP-AP, for example, showed an intense disruption of the epithelium and high degree of seminiferous tubule degeneration. Curiously, no morphological or morphometric alterations were observed in animals treated with captopril or BPP-11e [14]. These data have suggested that the alterations in the structure and function of the seminiferous epithelium in mice are dependent on their primary molecular structure and cannot be generalized for other BPPs [14].…”

“…Curiously, no morphological or morphometric alterations were observed in animals treated with captopril or BPP-11e [14]. These data have suggested that the alterations in the structure and function of the seminiferous epithelium in mice are dependent on their primary molecular structure and cannot be generalized for other BPPs [14]. In the current study, we investigated the toxicological effects of LMWF obtained from B. jararaca snake venom, on the dynamic and structure of the seminiferous epithelium in mice following intratesticular (i.t.)…”

“…The vehicle (same volume of 0.91% w/v NaCl) was also administrated in the testicular parenchyma of the right testis of the same animal (control). Each sample was administered using a 0.5-mL syringe and a 30-gauge needle (Ultra-Fine Short Needle, BD, Canada) [14]. Subsequently, the animals were maintained in the animal house for seven days and then were euthanized using CO 2 asphyxiation.…”

“…Intratesticular administration influence of LMWF in the morphology of the seminiferous tubules was analyzed by semiquantitative histopathological analysis of the seminiferous tubules [14]. Seminiferous tubules of all treatments were classified into four categories: normal tubules (T1); hypospermatogenic tubules (T2); arrested maturation (T3); and tubules containing spermatogonia and Sertoli cells or Sertoli-cell-only tubules (T4).…”

“…However, this peptide showed inhibitory effects on the spermiogenesis without affecting the permeability of blood-testis barrier (BTB) and the distribution of claudin-1 in the male Swiss mice [13]. Additionally, the effects of different synthetic peptides [BPP-10c (<ENWPHQIPP), BPP-11e (<EARPPHPPIPP), BPP-AP (<EARPPHPPIPPAP)] and captopril were evaluated after injection into the testicular parenchyma (120 nmol/dose per testis) [14]. BPP-10c and BPP-AP, for example, showed an intense disruption of the epithelium and high degree of seminiferous tubule degeneration.…”