Search

Background information Diabetes-induced testicular dysfunction is characterised by abnormal apoptosis of spermatogenic cells, but the underlying mechanism is poorly understood. This study aimed to investigate the roles of clusterin (CLU) in testicular damage associated with diabetes pathogenesis, as well as the molecular mechanism. A rat diabetes model was established using streptozocin, and the mouse spermatogenic cell line GC-1 spg was treated with high glucose as a cellular model. CLU was overexpressed in GC-1 spg cells, followed by detection of serum testosterone, cell proliferation, cell apoptosis and autophagy. Results CLU expression was significantly reduced and LC3 expression was elevated in testis tissues in the rat diabetes model and high glucose-treated GC-1 spg cells. High glucose led to suppressed viability, enhanced apoptosis, reduced Bcl-2 expression, elevated Bax expression and cleavage of Caspase-3/-9 in GC-1 spg cells, and these effects were abrogated by CLU overexpression. Additionally, CLU overexpression repressed LC3 and Beclin-1 expression, reduced the LC3II/LC3I ratio and promoted p62 expression in GC-1 spg cells in the presence of high glucose, and these effects were all mitigated by rapamycin treatment. Inhibition of PI3K/AKT/mTOR signalling with LY294002 activated autophagy in CLU-overexpressing GC-1 spg cells under high glucose conditions. CLU overexpression repressed autophagy and alleviated testicular damage in diabetic rats, which was also abrogated by LY294002 treatment. Conclusions CLU expression is suppressed during diabetes-induced testicular damage, whereas CLU overexpression alleviates diabetes-induced testicular damage by activating PI3K/AKT/mTOR signalling to inhibit autophagy and further repress spermatogenic cell apoptosis.

Coal-burning type of endemic fluorosis is capable of causing damage to both the male and female reproductive systems. The effects of coal-burning type of endemic fluorosis on the male reproductive system are mainly manifested in the following aspects: changes in testicular tissue structure, disturbances in sex hormone levels, imbalance in the testicular oxidative/antioxidant system, elevated apoptosis rate of spermatogenic cells, and reduced semen quality. The effects of coal-burning type of endemic fluorosis on the female reproductive system are mainly manifested in the following aspects: fluorosis interferes with the synthesis and secretion of sex hormones; coal-burning type of endemic fluorosis destroys the structure and function of reproductive organs such as the uterus and ovaries; fluorosis affects the structure and function of the placenta, and leads to fetal dysplasia, malformation, and even stillbirth.

To study the effect of taurine on the reproductive toxicity damage induced by formaldehyde (FM) in adult male rats.Forty-eight SD adult male rats were equally randomized into a normal control, an FM poisoning (FMP), a taurine intervention (TI), and an TI+FMP group. The control rats were given normal diet and gavage of saline, the rats of the FMP group treated intraperitoneally with FM at 10 mg/kg qd alt, those of the TI group intragastrically with taurine at 100 mg/kg qd, and those of the TI+FMP group with both FM and taurine at the above doses. After 30 days of treatment, the blood of the abdominal cardinal vein of the rats was extracted for measurement of the levels of serum hormones, the body weight, testis weight and testicular coefficient obtained, the testis tissue subjected to HE staining, and the expressions of Bcl-2 and Bax determined by Western blot.There were no statistically significant differences among the four groups of rats in the body weight, testis weight or testicular coefficient (P0.05). The rats in the FMP group showed obviously decreased testicular spermatogenic cells and disordered layers and loose structure of seminiferous tubules, which were basically restored to normal after taurine intervention. Compared with the normal controls, the animals of the TI group exhibited no significant abnormality, but those of the FMP group presented markedly reduced levels of serum T, LH and FSH (P0.05), and dramatically increased level of Gonadotropin-releasing hormone (GnRH) (P0.01). The levels of serum hormones were all significantly improved (P0.05) and that of the apoptotic protein Bax basically returned to normal (P0.05) after taurine intervention.Taurine has a certain protective effect against male reproductive toxicity caused by formaldehyde.

Although fluoride has been widely used in toothpaste, mouthwash, and drinking water to prevent dental caries, the excessive intake of fluoride can cause fluorosis which is associated with dental, skeletal, and soft tissue fluorosis. Recent evidences have drawn the attention to its adverse effects on male reproductive system that include spermatogenesis defect, sperm count loss, and sperm maturation impairment. Fluoride induces oxidative stress through the activation of mitogen activated protein kinase (MAPK) cascade which can lead to cell apoptosis. Vitamin E (VE) and lycopene are two common antioxidants, being protective to reactive oxygen species (ROS)-induced toxic effects. However, whether and how these two antioxidants prevent fluoride-induced spermatogenic cell apoptosis are largely unknown. In the present study, a male rat model for coal burning fluorosis was established and the histological lesions and spermatogenic cell apoptosis in rat testes were observed. The decreased expression of clusterin, a heterodimeric glycoprotein reported to regulate spermatogenic cell apoptosis, was detected in fluoride-treated rat testes. Interestingly, the co-administration with VE or lycopene reduced fluorosis-mediated testicular toxicity and rescued clusterin expression. Further, fluoride caused the enhanced Jun N-terminal kinase (JNK, c-Jun) and extracellular signal-regulated protein kinase (ERK) phosphorylation, which was reduced by VE or lycopene. Thus, VE and lycopene prevent coal burning fluorosis-induced spermatogenic cell apoptosis through the suppression of oxidative stress-mediated JNK and ERK signaling pathway, which could be an alternative therapeutic strategy for the treatment of fluorosis.

Fluorosis of coal burning is a new type of endemic fluorosis in China, which affects the male reproductive system. Furthermore, the content of fluoride in the semen, sperm mortality, sperm concentration and the incidence of infertility are higher in severe fluorosis areas than in mild- and non-fluorosis areas, so are the levels of serum follicle-stimulating hormone and luteinizing hormone. However, the levels of inhibin B, serum testosterone and estradiol show different degrees of reduction in severe fluorosis areas. Accordingly, fluorosis of coal burning, just like other endemic fluorosis, may affect the structure of male reproductive organs, the generation of sperm and reproductive endocrinology, resulting in the decline of men's reproductive ability.

To explore the effect of endemic fluoride poisoning caused by coal burning on the oxidative stress in rat testis.Totally 40 male SD rats were equally randomized into four groups control group, low fluorosis group, middle fluorosis group, and high fluorosis group. Rats in all three fluorosis groups were fed with corn dried by burning coal obtained from endemic fluorosis areas with high fluoride, and thus the animal models of fluorosis were established. After 120 and 180 days, all the rats were sacrificed. Testis tissues were stained with hematoxylin eosin and observed under light microscope. The malonaldehyde (MDA) content, superoxide dismutase (SOD) activity, total nitric oxide synthase (TNOS), and inducible nitric oxidase synthase (iNOS) were measured by biochemical methods in the testis tissues. The content of NaF in testis was measured by fluorine selective electrode.The rat fluorosis models were successfully established. The fluoride content in testis was significantly increased in all the fluorosis groups(P0.01). Testicular structures were damaged in all of fluoride groups. The TNOS, iNOS activities, and MDA content of each fluoride group were significantly higher than that of the control group on day 120 and 180 (P0.05 or 0.01 ). The TNOS, iNOS activities, and MDA content significantly increased in a dose dependent manner (P0.05 or 0.01). The SOD activities significantly decreased in all the fluoride groups (P0.05 or 0.01).Endemic fluoride poisoning caused by coal burning can cause disorders in the oxidative system and antioxidative system in rat testis. The oxidative stress may play an important role in the fluorides induced reproductive toxicity in male rats.