Effects of Streptozotocin Induced Diabetes on One-Carbon Cycle and Sperm Function

Abstract

Objective: Diabetic men suffer an increased risk of infertility associated with signs of oxidative damage and decreasedmethylation in sperm pointing to a deficit of the one-carbon cycle (1CC). We aimed to investigate this deficit using micemodels (type 1 and 2) of streptozotocin-induced diabetes.Materials and Methods: In this experimental study, 50 male mice, aged eight weeks, were divided randomly intofour groups: sham, control, type 1 diabetes mellitus (DM1), and DM2. The DM1 group was fed a normal diet (ND) foreight weeks, followed by five consecutive days of intraperitoneal administration of Streptozotocin (STZ, 50 mg/kg bodyweight). The DM2 group was fed a high-fat diet (HFD) for eight weeks, followed by a single intraperitoneal injectionof STZ (100 mg/kg). After twelve weeks, all the mice were euthanized, and study parameters assessed. In the shamgroup, citrate buffer as an STZ solvent was injected.Results: Both types of diabetic animals had serious impairment of spermatogenesis backed by increased DNA damage(P=0.000) and decreased chromatin methylation (percent: P=0.019; intensity: P=0.001) and maturation (P=0.000).The 1CC was deeply disturbed with increased homocysteine (P=0.000) and decreased availability of carbon units[methionine (P=0.000), serine (P=0.088), folate (P=0.016), B12 (P=0.025)] to feed methylations.Conclusion: We have observed a distinct impairment of 1CC within the testes of individuals with diabetes. Wespeculate that this impairment may be linked to inadequate intracellular glucose and diminished carbon unit supplyassociated with diabetes. As a result, interventions focusing on enhancing glucose uptake into sperm cells and providingsupplementary methyl donors have the potential to improve fertility issues in diabetic patients. However, additionalclinical testing is required to validate these hypotheses.

Keywords

• diabetes
• glucose
• methylations
• one-carbon cycle
• spermatogenesis