Adropin mitigates reproductive and metabolic dysfunctions in streptozotocin induced hyperglycemic mouse

Hyperglycemia is the predominant endocrine and metabolic disorder, resulting in infertility in males. Adropin, a hepatokine, is a well-known insulin sensitizer that regulates glucose and lipid homeostasis. Our recent reports demonstrated the vital role of adropin in the regulation of testicular activity but its role in testicular function during pathological condition like hyperglycemia is not yet studied. Therefore, this study aimed to explore the effect of adropin treatment on reproductive and metabolic dysfunctions in hyperglycemic mice. Hyperglycemia was induced by streptozotocin (55 mg/kg body weight; i.p.) treatment followed by treatment with either adropin (450 nmol/kg body weight; i.p.) or metformin (500 mg/kg body weight; orally) for a period of 15 days. Treatment to hyperglycemic mice enhanced insulin sensitivity by increasing insulin receptor expression in the testis and decreasing HOMA-IR and circulating glucose level. Adropin treatment to hyperglycemic mice increased the production of testicular testosterone by promoting the expression of steroidogenic proteins. Moreover, adropin treatment also enhanced the proliferation and survival of testicular germ cells by increasing PCNA expression and decreasing BAX/Bcl2 ratio and TUNEL positive cells in the testis of hyperglycemic mice. Flow-cytometric analysis revealed the increased number of advance germ cells in adropin treated hyperglycemic mice. Notably, adropin treatment is more effective than metformin in restoring reproductive functions in hyperglycemic mice that is evident by the reestablishment of the testicular histoarchitecture and increased synthesis of testosterone in the testes. These findings suggest that adropin may serve as a viable therapeutic alternative to mitigate the hyperglycemia-associated testicular dysfunction.