The protective effect of regucalcin against radiation-induced testicular damage

• Autor(a) principal: Silva, Ana Manuela dos Santos
• Data de Publicação: 2015
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10400.6/6061
• topic: Apoptose; Dano Testicular; Epidídimo; Espermatogénese; Espermatozóides; Oncofertilidade Masculina; Preservação da Fertilidade; Radioterapia; Regucalcina; Testículo; Domínio/Área Científica::Ciências Médicas::Ciências Biomédicas

Testicular cancer is the most common malignancy among young men, and radiation therapy is a generally used as treatment. However, the exposure to radiation has several adverse effects on male fertility. Considering the high survival rates and the age of incidence of this malignancy, it is mandatory to identify effective strategies protecting against radiation-induced testicular damage. Regucalcin (RGN) is a calcium (Ca2+)-binding protein that is broadly expressed in the male reproductive tract. Several studies have demonstrated RGN ability suppressing cell death in different cell types. Previously, our research group showed that RGN overexpression had beneficial effects on spermatogenesis by suppressing chemical-induced apoptosis. Moreover, RGN is upregulated in radioresistant cell lines, suggesting that it also can protect from radiation damage. The present work aimed to evaluate whether RGN may play a role in spermatogenesis recovery after radiation treatment. For this purpose, transgenic rats overexpressing RGN (Tg-RGN) and their wild-type (Wt) counterparts were exposed to X-rays. At ten weeks of recovery after irradiation, the testicular status and the epididymal sperm parameters were evaluated. The expression of RGN and several cell cycle and apoptosis regulators was also evaluated. In addition, the enzymatic activity of caspase-3 was measured. Upon radiation treatment and ten weeks of recovery, both the testicular status and sperm parameters seem to have been less affected by X-rays in Tg-RGN. We also found a diminished expression of p53 and p21, which may indicate the reinitiating of spermatogenesis. Moreover, the reduced activity of caspase-3 detected in Tg-RGN is in accordance with low levels of caspase-8 and increased Bcl-2/Bax ratio, suggesting that these animals are more resistant to testicular apoptosis in response to radiation. RGN expression was significantly enhanced in Wt rats after irradiation, supporting its involvement in the anti-apoptotic response. Altogether, the present findings point out a protective role for RGN overexpression against radiation-induced testicular damage.