Effect of metformin on germ cell-specific apoptosis, oxidative stress and epididymal sperm quality after testicular torsion/detorsion in rats

Abstract

The study was designed to evaluate the effects of metformin on apoptosis and epididymal sperm quality in a rat testicular ischaemia/reperfusion (I/R) injury model. A total of 72 male rats were divided into four groups (n = 18 for each group): group 1 (sham-operated group), group 2 (metformin group), group 3 (torsion/detorsion [T/D] + saline) and group 4 (T/D + 300 mg kg metformin). Testicular torsion was achieved by rotating the right testis 720° in a clockwise direction for 1 hr. Tissue malondialdehyde (MDA) level and caspase-3 activity increased and the activities of catalase, superoxide dismutase and glutathione peroxidase decreased in comparison with sham-operated group 4 hr after detorsion (p < .001). In six rats of each group 24 hr after detorsion, histopathological changes and germ cell apoptosis were significantly deteriorated by measuring mean of seminiferous tubule diameters (MSTD) and TUNEL test. Moreover, 30 days after T/D, sperm concentration and motility were examined in six animals per group. Metformin pre-treatment reduced MDA and caspase-3 levels and normalised antioxidant enzyme activities 4 hr after detorsion, and germ cell apoptosis was significantly decreased, and the MSTD, as well as sperm functions, was significantly improved. Reduction in oxidative stress and apoptosis may have a major role in cytoprotective effects of metformin.

The effect of vitamin C on the gene expression profile of sperm protamines in the male partners of couples with recurrent pregnancy loss: A randomized clinical trial

“…Deemeh et al [38] revealed that male partners of couples with RPL had high levels of protamine deficiency. As DNA integrity plays a key role in sperm function, it can be a better predictor of sperm fertility potential than conventional sperm parameters [39]. The results of three studies conducted by Aoki et al showed that more severe protamine deficiency was related to DNA damage in infertile men [11,14,40].…”

“…The results of three studies conducted by Aoki et al showed that more severe protamine deficiency was related to DNA damage in infertile men [11,14,40]. Previous research demonstrated a positive correlation between reactive oxygen species levels and apoptosis rate in seminal plasma [39,41]. Antioxidants have been observed to reduce apoptosis in testicular cells and to improve sperm quality [42].…”

Down‐regulation of steroidogenesis‐related genes and its accompanying fertility decline in streptozotocin‐induced diabetic male rats: ameliorative effect of metformin

“…For example, metformin and clomifene are currently being prescribed for females for the management of polycystic ovarian syndrome (PCOS), with positive results (Palomba et al ., ). Also, experimental studies have found metformin beneficial in protecting the hippocampus (Ge et al ., ), heart (Apaijai et al ., ), and testis (Asghari et al ., ; Ghasemnejad‐Berenji et al ., ) from ischemia–reperfusion injury. It also increases androgen and estrogen receptor expressions in the testis and increases serum testosterone level in diabetic rats (Nasrolahi et al ., ; Ayuob et al ., ).…”

Tyrosol prevents AlCl3induced male reproductive damage by suppressing apoptosis and activating the Nrf‐2/HO‐1 pathway

“…By means of this mechanism, Al reduces pituitary gonadotropin release, causing a decrease in the sperm count (Cheraghi, Golkar, Roshanaei, & Alani, ). Oxidative damage causes injuries in the testicular tissue and reduces the germ cells (Ghasemnejad‐Berenji et al, ). Reactive oxygen compounds (ROS), emerging due to the oxidative damage, play a central role in a series of pathological conditions in association with the environmental factors including inflammation, toxicity and endocrine disorders.…”