miR-27b-3p Improved High Glucose-Induced Spermatogenic Cell Damage via Regulating Gfpt1/HBP Signaling

<b><i>Introduction:</i></b> Diabetes mellitus (DM)-induced testicular damage is characterized by abnormal apoptosis of spermatogenic cells. Here, we clarified the roles and the molecular mechanism of microRNA (miR)-27b-3p in high glucose (HG)-induced spermatogenic cell damage. <b><i>Methods:</i></b> GC-1 spg cells were treated with 30 mmol/L glucose for 24 h. Cell viability was assessed by 2.3 3-(4, 5-dimethylthiazolyl2)-2, 5-diphenyltetrazolium bromide (MTT) assay. And, levels of O-linked N-acetylglucosamine (OGT), apoptosis-related proteins, and autophagy-related proteins were evaluated using Western blot. Levels of tumor necrosis factor-α (TNF-α), IL-1β, IL-6, and UDP-N-acetylglucosamine (UDP-GlcNAc) were assessed by enzyme linked immunosorbent (ELISA) assay. Levels of reactive oxygen species (ROS), malonic dialdehyde (MDA) and activity of superoxide dismutase (SOD) in cells were determined using kits. Cell apoptosis was determined using flow cytometry assay. Besides, dual luciferase reporter assay was employed to verify the binding relationship between miR-27b-3p and glutamine-fructose-6-phosphate transaminase 1 (Gfpt1). <b><i>Results:</i></b> miR-27b-3p was markedly downregulated in HG-treated GC-1 spg cells. HG treatment caused decreased cell viability, increased oxidative stress and inflammation, and induced autophagy and apoptosis, which were abolished by miR-27b-3p overexpression. miR-27b-3p suppressed the activation of hexosamine biosynthetic pathway (HBP) signaling in HG-treated spermatogenic cells. miR-27b-3p directly bound to Gfpt1 and negatively regulated its expression. <b><i>Conclusion:</i></b> miR-27b-3p could improve HG-induced spermatogenic cell damage via regulating Gfpt1/HBP signaling, providing a new treatment strategy for the treatment of DM-induced testicular damage.

Food-Derived High Arginine Peptides Promote Spermatogenesis Recovery in Busulfan Treated Mice

Food-derived peptides with high arginine content have important applications in medicine and food industries, but their potential application in the treatment of oligoasthenospermia remains elusive. Here, we report that high-arginine peptides, such as Oyster peptides and Perilla purple peptides were able to promote spermatogenesis recovery in busulfan-treated mice. We found that both Opp and Ppp could increase sperm concentration and motility after busulfan-induced testicular damage in mice. Further research revealed that Opp and Ppp might promote spermatogonia proliferation, which improved blood-testis barrier recovery between Sertoli cells. Taken together, these high-arginine peptides might be used as a medication or therapeutic component of a diet prescription to improve the fertility of some oligoasthenospermia patients.

Allopurinol and Febuxostat Equally Attenuate Methotrexate-Induced Testicular Injury In Rats Via Activation Of EGF/ ERK1/2/HO‐1 Signaling Pathway.

Methotrexate (MTX) is commonly used in the management of several malignancies and autoimmune disorders; however, testicular damage is one of the most detrimental effects of MTX administration. In the current study, we evaluated the possible protective effect of xanthine oxidase inhibitors either purine analogue; allopurinol (ALL) or non-purine analogue; febuxostat (FEB) in testicular injury induced by MTX in rats. Gonadotoxicity was induced by a single dose of MTX (20 mg/kg, i.p.). ALL and FEB were administered orally in the following daily doses (100, 10 mg/kg, respectively) for 15 days. Total and free testosterone were measured in serum. In addition, total antioxidant capacity (TAC), epidermal growth factor (EGF), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), extracellular signal-regulating kinase1/2 (ERK1/2), and nitric oxide (NO) end products were measured in testicular tissues. At the same time, immunoexpression of HO-1in testicular tissue was measured. Histopathological examination was done. ALL and FEB increased total and free serum testosterone. Both drugs showed a significant reduction in testicular MDA, NO, TNF-α levels with an increase in TAC, EGF, and ERK1/2 levels in testicular tissue. Furthermore, both drugs enhanced HO-1 immunoexpression in testicular tissue. All these findings were parallel to the preservation of normal testicular architecture in rats treated with ALL and FEB. In conclusion, All and FEB were protective against testicular damage induced by MTX through anti-inflammatory, anti-apoptotic, and antioxidant actions which might be through activation of the EGF/ERK1/2/HO-1 pathway. At the same time, no significant difference between ALL and FEB was noticed in this protective effect.