Crocetin Mitigates Irradiation Injury in an In Vitro Model of the Pubertal Testis: Focus on Biological Effects and Molecular Mechanisms
Giulia Rossi,
Martina Placidi,
Chiara Castellini,
Francesco Rea,
Settimio D'Andrea,
Gonzalo Luis Alonso,
Giovanni Luca Gravina,
Carla Tatone,
Giovanna Di Emidio,
Anna Maria D’Alessandro
Affiliations
Giulia Rossi
Lab of Reproductive Technologies, Department of Life, Health and Environmental Sciences, University of L’Aquila, 67100 L’Aquila, Italy
Martina Placidi
Lab of Reproductive Technologies, Department of Life, Health and Environmental Sciences, University of L’Aquila, 67100 L’Aquila, Italy
Chiara Castellini
Andrology Unit, Department of Life, Health and Environmental Sciences, University of L’Aquila, 67100 L’Aquila, Italy
Francesco Rea
Lab of Reproductive Technologies, Department of Life, Health and Environmental Sciences, University of L’Aquila, 67100 L’Aquila, Italy
Settimio D'Andrea
Andrology Unit, Department of Life, Health and Environmental Sciences, University of L’Aquila, 67100 L’Aquila, Italy
Gonzalo Luis Alonso
Química Agrícola, E.T.S.I. Agrónomos y Montes, Departamento de Ciencia y Tecnología Agroforestal y Genética, Universidad de Castilla-La Mancha, Avda. de España s/n, 02071 Albacete, Spain
Giovanni Luca Gravina
Laboratory of Radiobiology, Division of Radiotherapy, Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, 67100 L’Aquila, Italy
Carla Tatone
Lab of Reproductive Technologies, Department of Life, Health and Environmental Sciences, University of L’Aquila, 67100 L’Aquila, Italy
Giovanna Di Emidio
Lab of Reproductive Technologies, Department of Life, Health and Environmental Sciences, University of L’Aquila, 67100 L’Aquila, Italy
Anna Maria D’Alessandro
Lab of Nutritional Biochemistry, Department of Life, Health and Environmental Sciences, University of L’Aquila, 67100 L’Aquila, Italy
Infertility is a potential side effect of radiotherapy and significantly affects the quality of life for adolescent cancer survivors. Very few studies have addressed in pubertal models the mechanistic events that could be targeted to provide protection from gonadotoxicity and data on potential radioprotective treatments in this peculiar period of life are elusive. In this study, we utilized an in vitro model of the mouse pubertal testis to investigate the efficacy of crocetin to counteract ionizing radiation (IR)-induced injury and potential underlying mechanisms. Present experiments provide evidence that exposure of testis fragments from pubertal mice to 2 Gy X-rays induced extensive structural and cellular damage associated with overexpression of PARP1, PCNA, SOD2 and HuR and decreased levels of SIRT1 and catalase. A twenty-four hr exposure to 50 μM crocetin pre- and post-IR significantly reduced testis injury and modulated the response to DNA damage and oxidative stress. Nevertheless, crocetin treatment did not counteract the radiation-induced changes in the expression of SIRT1, p62 and LC3II. These results increase the knowledge of mechanisms underlying radiation damage in pubertal testis and establish the use of crocetin as a fertoprotective agent against IR deleterious effects in pubertal period.
