Adropin promotes testicular functions by modulating redox homeostasis in adult mouse

• Published in: Endocrine 2024-10, Vol.86 (1), p.428-440
• Main Authors: Tripathi, Shashank, Maurya, Shweta, Singh, Ajit
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants; Apoptosis - drug effects; BAX protein; Bcl-2 protein; Caspase-3; Cell differentiation; Cell proliferation; Diabetes; Endocrinology; Energy balance; Enzymatic activity; Enzyme-linked immunosorbent assay; Flow cytometry; Germ cells; Homeostasis; Homeostasis - drug effects; Humanities and Social Sciences; Intercellular Signaling Peptides and Proteins - metabolism; Internal Medicine; Male; Medicine; Medicine & Public Health; Mice; multidisciplinary; NF-κB protein; Nuclear transport; Original Article; Oxidation-Reduction - drug effects; Oxidative Stress - drug effects; Peptides - pharmacology; Redox potential; Science; Sperm Count; Spermatids; Spermatogenesis; Spermatogenesis - drug effects; Spermatogenesis - physiology; Steroidogenesis; Testes; Testis - drug effects; Testis - metabolism; Testosterone; Testosterone - blood; Testosterone - metabolism
• ISSN: 1559-0100; 1355-008X; 1559-0100
• DOI: 10.1007/s12020-024-03921-1

Purpose Adropin is an emerging metabolic hormone that has a role in regulating energy homeostasis. The present study aimed to explore the impact of adropin on redox homeostasis and its possible role in testicular functions in adult mouse testis. Methods Western blot, flow-cytometry, and TUNEL assay were performed to explore the impact of i ntra-testicular treatment of adropin (0.5 μg/testis) on testicular functions of adult mice. Hormonal assay was done by ELISA. Further, antioxidant enzyme activities were measured. Results Adropin treatment significantly increased the sperm count and testicular testosterone by increasing the expression of GPR19 and steroidogenic proteins. Also, adropin treatment reduced the oxidative/nitrosative stress by facilitating the translocation of NRF2 and inhibiting NF-κB into the nucleus of germ cells. Enhanced nuclear translocation of NRF2 leads to elevated biosynthesis of antioxidant enzymes, evident by increased HO-1, SOD, and catalase activity that ultimately resulted into declined LPO levels in adropin-treated mice testes. Furthermore, adropin decreased nuclear translocation of NF-κB in germ cells, that resulted into decreased NO production leading to decreased nitrosative stress. Adropin/GPR19 signaling significantly increased its differentiation, proliferation, and survival of germ cells by elevating the expression of PCNA and declining caspase 3, cleaved caspase 3 expression, Bax/Bcl2 ratio, and TUNEL-positive cells. FACS analysis revealed that adropin treatment enhances overall turnover of testicular cells leading to rise in production of advanced germ cells, notably spermatids. Conclusion The present study indicated that adropin improves testicular steroidogenesis, spermatogenesis via modulating redox potential and could be a promising target for treating testicular dysfunctions.