Diabetes Mellitus (DM) is an endocrine disorder that affects many systems, including the reproductive organs. Several studies in this field have shown a decrease in sperm quality, semen volume, sperm viability, motility and normal morphology. Hyperglycemia causes men infertility through testicular dysfunction. Forkhead O1 (FOXO1) contributes to glucose metabolism in obesity-associated type-2 diabetes. FOXO1 is the downstream molecule of the PI3K/Akt pathway and is negatively regulated by it. FOXO1, phosphorylated by Akt, translocates from the nucleus to the cytoplasm. After nuclear export, FOXO1 loses its transcription effect on DNA. The PI3K-Akt signaling pathway promotes glucose uptake by peripheral tissues and insulin secretion by pancreatic beta cells while FOXO1 induces gluconeogenesis enzymes and glucose production. Insulin and IGF-1 inhibit the FOXO1 pathway and therefore reduce gluconeogenesis in the liver. FOXO1 inhibition has been reported to improve insulin secretion from pancreatic β cells and reduce insulin resistance through an improvement in glucose homeostasis. FOXO1 is also a proapoptotic molecule that induces FasL and apoptosis of testicular tissue. Inhibited PI3K-Akt pathway and stimulation of the inflammatory cytokine IL-6 in diabetic mice leads to FOXO1 activation. FOXO1 promotes diabetes-induced spermatogenic dysfunction via apoptosis. An increased rate of apoptosis has also been noted in A1 spermatozoa of obesity. According to recent studies, apoptosis induction in spermatogenic cells is a major factor in male infertility. This review summarizes diabetes-associated FOXO1 pathway. Specific FOXO1 targeting therapies can improve obesity and diabetic complications on testicular tissue.
Anahtar Kelimeler: Apoptosis, FoxO1, Male infertility, Obesity, Diabetes mellitus
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