Lab of Reproductive Technologies, Department of Life, Health and Environmental Sciences, University of L'Aquila, 67100 L'Aquila, Italy.
Andrology Unit, Department of Life, Health and Environmental Sciences, University of L'Aquila, 67100 L'Aquila, Italy.
Molecules. 2021 Mar 17;26(6):1676. doi: 10.3390/molecules26061676.
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.
不育是放射治疗的潜在副作用，严重影响青少年癌症幸存者的生活质量。很少有研究在青春期模型中探讨可能针对性腺毒性的机制事件，并且在这个特殊的生命阶段，关于潜在的放射防护治疗的数据也难以捉摸。在这项研究中，我们利用体外的小鼠青春期睾丸模型来研究西红花酸对电离辐射（IR）诱导损伤的作用及其潜在的机制。目前的实验提供了证据，表明暴露于 2 Gy X 射线的青春期小鼠睾丸片段会引起广泛的结构和细胞损伤，这与 PARP1、PCNA、SOD2 和 HuR 的过度表达以及 SIRT1 和过氧化氢酶水平降低有关。在辐照前和辐照后 24 小时暴露于 50 μM 的西红花酸可以显著减少睾丸损伤，并调节对 DNA 损伤和氧化应激的反应。然而，西红花酸处理不能逆转辐射诱导的 SIRT1、p62 和 LC3II 表达的变化。这些结果增加了对青春期睾丸辐射损伤机制的了解，并确立了西红花酸作为一种生育保护剂，可防止青春期的 IR 有害影响。
