Abstract
BackgroundThe testis-specific isoform of angiotensin-converting enzyme (tACE) is exclusively expressed in germ cells during spermatogenesis. Although the exact role of tACE in male fertility is unknown, it clearly plays a critical function in spermatogenesis. The dipeptidase domain of tACE is identical to the C-terminal catalytic domain of somatic ACE (sACE). Bradykinin potentiating peptides (BPPs) from snake venoms are the first natural sACE inhibitors described and their structure–activity relationship studies were the basis for the development of antihypertensive drugs such as captopril. In recent years, it has been showed that a number of BPPs – including BPP-10c – are able to distinguish between the N- and C-active sites of sACE, what is not applicable to captopril. Considering the similarity between tACE and sACE (and since BPPs are able to distinguish between the two active sites of sACE), the effects of the BPP-10c and captopril on the structure and function of the seminiferous epithelium were characterized in the present study. BPP-10c and captopril were administered in male Swiss mice by intraperitoneal injection (4.7 μmol/kg for 15 days) and histological sections of testes were analyzed. Classification of seminiferous tubules and stage analysis were carried out for quantitative evaluation of germ cells of the seminiferous epithelium. The blood-testis barrier (BTB) permeability and distribution of claudin-1 in the seminiferous epithelium were analyzed by hypertonic fixative method and immunohistochemical analyses of testes, respectively.ResultsThe morphology of seminiferous tubules from animals treated with BPP-10c showed an intense disruption of the epithelium, presence of atypical multinucleated cells in the lumen and degenerated germ cells in the adluminal compartment. BPP-10c led to an increase in the number of round spermatids and total support capacity of Sertoli cell in stages I, V, VII/VIII of the seminiferous epithelium cycle, without affecting BTB permeability and the distribution of claudin-1 in the seminiferous epithelium. Interestingly, no morphological or morphometric alterations were observed in animals treated with captopril.ConclusionsThe major finding of the present study was that BPP-10c, and not captopril, modifies spermatogenesis by causing hyperplasia of round spermatids in stages I, V, and VII/VIII of the spermatogenic cycle.
Highlights
The testis-specific isoform of angiotensin-converting enzyme is exclusively expressed in germ cells during spermatogenesis
Effect of Bradykinin potentiating peptides (BPPs)-10c on the seminiferous epithelium in male adult mice The seminiferous tubules observed in animals treated with vehicle (Figure 1 – A) and captopril (Figure 1 – B) displayed normal testicular tissue with typical seminiferous epithelium after 15 days of treatment
The treatment with BPP-10c led to an increase in the number of round spermatids in stages I, V, VII/VIII (Table 1)
Summary
The testis-specific isoform of angiotensin-converting enzyme (tACE) is exclusively expressed in germ cells during spermatogenesis. Considering the similarity between tACE and sACE (and since BPPs are able to distinguish between the two active sites of sACE), the effects of the BPP-10c and captopril on the structure and function of the seminiferous epithelium were characterized in the present study. The blood-testis barrier (BTB) permeability and distribution of claudin-1 in the seminiferous epithelium were analyzed by hypertonic fixative method and immunohistochemical analyses of testes, respectively. Testis-specific isoform of angiotensin-converting enzyme (tACE) is exclusively expressed in maturing germ cells and spermatozoa, but not in Sertoli cells, Leydig cells or any other somatic cell in male adults, suggesting that it is related to the spermiogenesis process [4,5,6,7]. It has been reported that tACE is able to release the extracellular portion of glycosylphosphatidylinositol (GPI)-anchored proteins, and it is directly and implicated in egg fertilization by the sperm, independent of its peptidase activity [12,13]
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