Activation of Bcl-2-Caspase-9 Apoptosis Pathway in the Testis of Asthmatic Mice

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.

Ameliorative effect of taurine-chloramine in azathioprine-induced testicular damage; a deeper insight into the mechanism of protection

“…In agreement with our findings, Xu et al (2016) [ 39 ] documented an increase in the activity of Bcl-2/Caspase-9 apoptosis pathway in the testis of asthmatic mice subjected to apoptotic inducers like ovalbumin. The protective role of TAU-CL was highlighted by the changes in caspase-9 activity and Bcl-2 levels toward the control values, which –based on our histopathological analysis – appears to have restored normal numbers of germ cells during spermatogenesis.…”

Protective Effect of Taurine on Thiopurine-Induced Testicular Atrophy in Male Albino Rats

“…This dysregulation of the fine-tuned apoptotic pathway is considered one of the mechanisms of AZPinduced injury of the testicular function which might be the reason for decreased sperm viability and mobility. In alignment with our findings [56], documented an increase in the activity of Bcl2/Caspase-9 apoptosis pathway in the testis of mice subjected to apoptotic inducers.…”

Cuscuta chinensisflavonoids alleviate bisphenol A‐induced apoptosis of testicular cells in male mice offspring

“…There is a strong negative correlation between bax and bcl‐2, which is the main regulator of bcl‐2 activity. They play an important regulatory role in mitochondrial signal transduction pathway (Xu et al, ). In the current study, we found that BPA accelerated the apoptosis of testicular cells by increasing the expression of bax and inhibiting the expression of bcl‐2 in testis, impaired the normal function of testicular cells, and then affected the reproductive capacity of animals.…”