A bradykinin-potentiating peptide (BPP-10c) from Bothrops jararaca induces changes in seminiferous tubules

Background The 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 ident...

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Main Authors: Joyce M Gilio, Fernanda CV Portaro, Maria I Borella, Claudiana Lameu, Antonio CM Camargo, Carlos Alberto-Silva
Format: Article
Language:English
Published: SciELO 2013-11-01
Series:Journal of Venomous Animals and Toxins including Tropical Diseases
Subjects:
Online Access:http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1678-91992013000100316&lng=en&tlng=en
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author Joyce M Gilio
Fernanda CV Portaro
Maria I Borella
Claudiana Lameu
Antonio CM Camargo
Carlos Alberto-Silva
author_facet Joyce M Gilio
Fernanda CV Portaro
Maria I Borella
Claudiana Lameu
Antonio CM Camargo
Carlos Alberto-Silva
author_sort Joyce M Gilio
collection DOAJ
description Background The 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. Results The 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. Conclusions The 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.
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spelling doaj.art-0757fdce513042d98a106038f3a40ba62022-12-21T19:20:47ZengSciELOJournal of Venomous Animals and Toxins including Tropical Diseases1678-91992013-11-0119010.1186/1678-9199-19-28S1678-91992013000100316A bradykinin-potentiating peptide (BPP-10c) from Bothrops jararaca induces changes in seminiferous tubulesJoyce M GilioFernanda CV PortaroMaria I BorellaClaudiana LameuAntonio CM CamargoCarlos Alberto-SilvaBackground The 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. Results The 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. Conclusions The 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.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1678-91992013000100316&lng=en&tlng=enBradykinin-potentiating peptideSnake venomAngiotensin-converting enzymeTestisSeminiferous epithelium
spellingShingle Joyce M Gilio
Fernanda CV Portaro
Maria I Borella
Claudiana Lameu
Antonio CM Camargo
Carlos Alberto-Silva
A bradykinin-potentiating peptide (BPP-10c) from Bothrops jararaca induces changes in seminiferous tubules
Journal of Venomous Animals and Toxins including Tropical Diseases
Bradykinin-potentiating peptide
Snake venom
Angiotensin-converting enzyme
Testis
Seminiferous epithelium
title A bradykinin-potentiating peptide (BPP-10c) from Bothrops jararaca induces changes in seminiferous tubules
title_full A bradykinin-potentiating peptide (BPP-10c) from Bothrops jararaca induces changes in seminiferous tubules
title_fullStr A bradykinin-potentiating peptide (BPP-10c) from Bothrops jararaca induces changes in seminiferous tubules
title_full_unstemmed A bradykinin-potentiating peptide (BPP-10c) from Bothrops jararaca induces changes in seminiferous tubules
title_short A bradykinin-potentiating peptide (BPP-10c) from Bothrops jararaca induces changes in seminiferous tubules
title_sort bradykinin potentiating peptide bpp 10c from bothrops jararaca induces changes in seminiferous tubules
topic Bradykinin-potentiating peptide
Snake venom
Angiotensin-converting enzyme
Testis
Seminiferous epithelium
url http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1678-91992013000100316&lng=en&tlng=en
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