Toxic Effects and Possible Mechanisms of Deoxynivalenol Exposure on Sperm and Testicular Damage in BALB/c Mice

Abstract

Deoxynivalenol (DON, vomitoxin) is the most common mycotoxin in cereals and grains. DON contamination can cause a serious health threat to humans and farm animals. DON has been reported to exert significant toxicity effects on the male reproductive system. However, the causes and mechanisms underlying efforts of DON on sperm and testicular damage remain largely unclear. In the present study, we thoroughly investigated this issue. Eighty male BALB/c mice were randomly divided into a control group (n = 40) and DON treatment group (2.4 mg/kg of body weight, n = 40). The ratio of testes and seminal vesicle to body, sperm survival and motility, and morphology of sperm and testis were observed in DON-treated and control mice. In addition, the concentrations of reactive oxygen species (ROS) and malondialdehyde (MDA), the activities of superoxide dismutase (SOD) and glutathione (GSH), and also the expression levels of JNK/c-Jun signaling and apoptotic factors such as caspase-3, caspase-8, caspase-9, Bim, and Bid were analyzed and compared between the two groups. The results demonstrated that a single topical application of DON significantly increased the percentage of abnormal sperm and decreased the motility of sperm, indicating the sperms are damaged by DON. Additionally, the reduced relative body weight of testis and severe destruction of testicular morphology were observed. Moreover, the increased levels of ROS and MDA levels and decreased activities of SOD and GSH were found in testicular tissues, suggesting that oxidative stress is induced by DON treatment. Furthermore, DON upregulated the expression of stress-induced JNK/c-Jun signaling pathway proteins as well as JNK/c-Jun phosphorylation proteins. In addition, DON could enhance testicular apoptosis by increasing expression levels of apoptotic genes including Bim, cytochrome c, caspase 3, caspase 8, and caspase 9. These results suggest that DON exposure can cause sperm damage, oxidative stress, testicular apoptosis, and phosphorylation of JNK/c-Jun signaling pathway. The underlying mechanisms may be that DON induces sperm damage by exacerbating oxidative stress-mediated testicular apoptosis via JNK/c-Jun signaling pathway.

Effect of chronic stress on expression and secretion of seminal vesicle proteins in adult rats

“…Interestingly, the expressions of seminal caspases 3 and 9 observed in CS animals might be associated with the molecular apoptosis in the SVT. These results agree with previous reports about the presence of caspase 3 (do Nascimento et al, 2014;Jara et al, 2004;Tsounapi et al, 2017) and caspase 9 (Yang, Wang, et al, 2019;Yang, Zhang, et al, 2019) in male genital tracts under pathologic changes. Since TyrPho proteins essential for mature sperm physiology have been identified in testis, epididymis and seminal vesicle, many studies also demonstrated the changes of such proteins in CS testis Chaichun, Arun, Burawat, Kanla, & Iamsaard, 2017;Sawatpanich et al, 2018;Tongpan et al, 2019.…”

“…Furthermore, previous studies demonstrated overexpression of some SV proteins such as caspase 3 (do Nascimento, 2014;Jara, Carballada, & Esponda, 2004;Tsounapi et al, 2017) and caspase 9 (Yang, Wang, et al, 2019;Yang, Zhang, et al, 2019) in infertile animal models. Particularly, the changes of heat-shock protein 70 (Hsp70) are shown to associated with the reduction of SV components (Miyake, Muramaki, Kurahashi, Takenaka, & Fujisawa, 2008;Sahlén et al, 2010;Sundarraj, Raghunath, Panneerselvam, & Perumal, 2017;Tongpan et al, 2019).…”

Effects of the mycotoxin metabolite de‐epoxy‐deoxynivalenol (DOM‐1) on embryo development and sperm motility in cattle

“…Another major impact of DOM‐1 was on sperm motility in vitro. It has been shown that chronic in vivo DON exposure reduced circulating testosterone concentrations and increased germ cell degeneration and induced abnormal sperm morphology in rats (Sprando et al, 2005) and reduced sperm motility in mice (Yang et al, 2019). Here we demonstrate a significant reduction in progressive motility of bovine sperm after 8 h exposure to DOM‐1 in vitro.…”

Testicular quantitative ultrasound: A noninvasive monitoring method for evaluating spermatogenic function in busulfan‐induced testicular injury mouse models

“…Busulfan-induced testicular injury mouse models are widely used as powerful tools for experiments involving spermatogonial stem cell transplantation, new treatments for nonobstructive azoospermia and preserving male fertility after chemotherapy, in which the noninvasive and dynamic evaluation of spermatogenic function is desirable (Ganguli et al, 2016;Sharma et al, 2019;Zhao et al, 2020). In The reduction in the number of germ cells in the busulfan-induced testicular injury model can lead to a decrease in the testicle-to-body weight ratio (Karna et al, 2019;Yang et al, 2019). Measurement of the testicle-to-body weight ratio is easy and enables comparison, but it can reflect only overall changes in the testes.…”

“…Busulfan-induced testicular injury mouse models are commonly used for experiments on spermatogonial stem cell transplantation, treatments for azoospermia due to spermatogenic failure and preserving male fertility after chemotherapy, in which evaluating spermatogenic function is essential (Ganguli et al, 2016;Sharma et al, 2019;Zhao et al, 2020). To evaluate spermatogenic function after busulfan treatment, several parameters, including the testicle-to-body weight ratio, percentage of tubules with spermatogenic cells and seminiferous tubule diameter, have been used (Karna et al, 2019;Udefa et al, 2020;Yang et al, 2019). However, all of these parameters have the same limitations.…”