Abstract
BackgroundApoptosis plays a critical role in controlling the proliferation and differentiation of germ cells during spermatogenesis. Dysregulation of the fine-tuned balance may lead to the onset of testicular diseases. In this study, we investigated the activation status of apoptosis pathways in the testicular tissues under the background of an asthmatic mouse model.MethodsTen BALB/c mice were divided into two groups: the acute asthma group and the control group. In the acute asthma group, ovalbumin (OVA)-sensitized mice were challenged with aerosolized OVA for 7 days, while the control group was treated with physiological saline. After that, both epididymis and testis were collected to determine the sperm count and motility. Apoptosis in the testis was evaluated by DNA ladder, immunochemistry and further by PCR array of apoptosis-related genes. Finally, the cleavage of caspase-3 and poly ADP-ribose polymerase (PARP) was determined by western blot and the enzymatic activities of caspase-9 and 3/7 were assessed using Caspase-Glo kits.ResultsCompared with control mice, significant decreases in the body weight, testis weight, sperm count and motility were seen in the experimental group. DNA ladder and immunochemistry showed significant increase in apoptotic index of the asthmatic testis, whereas a decrease in mRNA expression of Bcl-2 and increases in Bax, BNIP3, caspase-9, and AIF were observed in the asthma group. Furthermore, protein levels of AIF were significantly upregulated, while the translational expression of Bcl-2 was downregulated markedly. Consistently, caspase-9 activity in the testis of asthma mice was significantly higher than that of the control group.ConclusionCollectively, these results showed that Bcl-2-caspase-9 apoptosis pathway was clearly activated in the testis of asthmatic mice with the increased expression of apoptosis-related genes and proteins. To our knowledge, this is the first report demonstrating that asthma could lead to the activation of the mitochondrial apoptosis signaling pathway in the mouse testis.
Highlights
Asthma is a common respiratory disorder with significant morbidity and mortality worldwide
Mice rendered allergic to OVA have been widely studied, and they serve as a prototypic asthma pathogenesis model [20]
As downstream events of apoptosis, we determined the enzymatic activity of caspase-9 and caspase-3/7, together with the cleavage of caspase-3 and poly ADPribose polymerase (PARP). These results demonstrate that the caspase apoptosis pathway is markedly activated in asthmatic testis compared with the control group, which might be the reason for decreased sperm viability and mobility
Summary
Asthma is a common respiratory disorder with significant morbidity and mortality worldwide. Characterized by airway inflammation, the disease involves multiple biological pathways including infiltration of T lymphocytes and eosinophils, increased secretion of pro-inflammatory cytokines, and reversible obstruction of bronchial tubes [3]. It is well established that the persistence of airway inflammation depends on a decrease in apoptosis of activated eosinophils and T lymphocytes [4]. Surviving T cells and eosinophils cooperate to induce bronchial epithelial cell apoptosis through secretion of IFN-gamma and TNF-alpha [5,6]. Asthmatic bronchial epithelium is more susceptible to oxidant-induced apoptosis [7]. Increased apoptosis of peripheral blood mononuclear cells was observed in patients with allergic asthma [9,10]. We investigated the activation status of apoptosis pathways in the testicular tissues under the background of an asthmatic mouse model.
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