4.7 Article

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

Journal

LIFE SCIENCES
Volume 164, Issue -, Pages 31-41

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2016.09.003

Keywords

Radiation therapy; Male fertility preservation; Regucalcin; Testicular damage

Funding

  1. FEDER funds through the POCI - COMPETE - Operational Programme Competitiveness and Internationalisation in Axis I - Strengthening research, technological development and innovation [007491]
  2. National Funds by FCT - Foundation for Science and Technology [UID/Multi/00709]
  3. FCT [SFRH/BPD/104820/2014]

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Aims: 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 Main methods: Transgenic rats overexpressing RGN (Tg-RGN) and their wild-type (Wt) counterparts were exposed to a single dose of X-rays (6 Gy), and atten 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. Key findings: 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. Significance: 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. (C) 2016 Elsevier Inc. All rights reserved.

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