Alberto-Silva Carlos, Gilio Joyce M, Portaro Fernanda C V, Querobino Samyr M, Camargo Antonio C M
Center for Natural and Humanities Sciences (CCNH), Federal University of ABC (UFABC), R. Santa Adélia, 166, Santo André, SP CEP 09210-170 Brazil.
Center for Applied Toxinology, Butantan Institute, São Paulo, SP Brazil.
J Venom Anim Toxins Incl Trop Dis. 2015 Aug 4;21:27. doi: 10.1186/s40409-015-0030-y. eCollection 2015.
Considering 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.
The 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.
BPP-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.
The 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.
考虑到血管紧张素转换酶的睾丸特异性同工型与体细胞血管紧张素转换酶的C末端催化结构域之间的相似性,以及其天然抑制剂(称为缓激肽增强肽,BPPs)的结构和功能变异性,评估了不同合成肽BPP-10c(<ENWPHQIPP)、BPP-11e(<EARPPHPPIPP)、BPP-AP(<EARPPHPPIPPAP)和卡托普利对雄性小鼠生精上皮的影响。
成年动物通过向睾丸实质内注射,接受合成肽或卡托普利(每只睾丸120 nmol/剂量)中的一种。7天后,处死小鼠,收集睾丸进行组织病理学评估。
BPP-10c和BPP-AP表现出上皮的强烈破坏,管腔内存在非典型多核细胞,生精小管高度退化,尤其是在接受BPP-AP治疗的动物中。此外,两种合成肽均导致生精周期I、V和VII/VIII阶段的精母细胞和圆形精子细胞数量、生精上皮厚度和生精小管管腔直径显著减少。有趣的是,在用卡托普利或BPP-11e治疗的动物中未观察到形态学或形态计量学改变。
本研究的主要发现是,BPP-10c和BPP-AP对生精上皮的已证实作用取决于它们的一级结构,不能外推到其他BPPs。