The protective effect of regucalcin against radiation-induced damage in testicular cells

• Published in: Life sciences (1973) 2016-11, Vol.164, p.31-41
• Main Authors: Silva, Ana M.S., Correia, Sara, Casalta-Lopes, João E., Mamede, Ana C., Cavaco, José E.B., Botelho, Maria F., Socorro, Sílvia, Maia, Cláudio J.
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; BAX protein; Bcl-2 protein; Blotting, Western; Calcium-Binding Proteins - genetics; Calcium-Binding Proteins - metabolism; Caspase; Caspase-3; Caspase-8; Caspases - metabolism; Cell cycle; Effects; Enzymatic activity; Enzyme Activation - drug effects; Enzyme Activation - radiation effects; Fertility; Gene Expression; Immunohistochemistry; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - metabolism; Irradiation; Male; Male fertility preservation; Preservation; Proteins; Radiation; Radiation damage; Radiation effects; Radiation therapy; Rats; Rats, Sprague-Dawley; Rats, Transgenic; Regucalcin; Regulators; Reproductive system; Sperm; Spermatogenesis; Spermatozoa - drug effects; Spermatozoa - radiation effects; Studies; Testes; Testicular damage; Testis - metabolism; Testis - radiation effects; Viability
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2016.09.003

Regucalcin (RGN), a protein broadly expressed in the male reproductive tract, has shown to have beneficial effects on spermatogenesis suppressing chemical-induced apoptosis. This study aimed to evaluate whether RGN overexpression ameliorates the spermatogenic phenotype after radiation treatment. Transgenic rats overexpressing RGN (Tg-RGN) and their wild-type (Wt) counterparts were exposed to a single dose of X-rays (6Gy), and at ten weeks after irradiation, the testicular status and the epididymal sperm parameters were evaluated. The expression of RGN and several cell cycle and apoptosis regulators, the enzymatic activity of caspase-3, and RGN immunostaining were also assessed. Tg-RGN animals displayed higher gonadosomatic index, and augmented sperm viability and motility relatively to their Wt counterparts after irradiation, as well as higher frequency of normal sperm morphology and a diminished incidence of head-defects. The differences in reproductive parameters were underpinned by a lower rate of apoptosis, as evidenced by the reduced activity of caspase-3, lower levels of caspase-8, and increased Bcl-2/Bax ratio in the testis of Tg-RGN animals. Supporting the involvement of RGN in the anti-apoptotic response, an enhanced expression of RGN was observed in irradiated rats. Transgenic-overexpression of RGN protected against radiation-induced testicular damage, which strengthens the role of this protein protecting cells from the damage of external agents. These findings also indicated that the modulation of RGN testicular levels would be a mechanism for fertility preservation in men undergoing oncological treatment.