研究动态
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白藜芦醇缓解了多柔比星对小鼠卵巢的损伤。

Resveratrol alleviates doxorubicin-induced damage in mice ovary.

发表日期:2023 Mar 14
作者: Yamila Herrero, Candela Velázquez, Natalia Pascuali, María May, Dalhia Abramovich, Leopoldina Scotti, Fernanda Parborell
来源: ANTIOXIDANTS & REDOX SIGNALING

摘要:

虽然卵母细胞和胚胎冷冻可以帮助某些因癌症治疗导致不孕不育的患者实现妊娠,但是开发有效的治疗策略来保护卵巢在化疗期间的功能将是一项重大的优势。本研究旨在分析白藜芦醇治疗(Res)是否可以使用小鼠早期卵巢衰竭模型保护卵巢功能,以防止多柔比星(Doxo)诱导的卵巢毒性。Res(7和15 mg / kg)增加了初级和环形卵泡的百分比,同时降低了闭鞘卵泡的百分比,与Doxo独自使用相比。与Doxo组相比,Res保留了原始卵泡的数量,但与对照组相比并没有改变。Res治疗使AMH阳性卵泡的数量增加,与Doxo单独使用相比。与Doxo独自使用相比,Res在卵泡细胞中增加了增殖指数,并减少了Doxo独立的卵泡DNA损伤和凋亡。此外,Doxo的使用会导致卵巢内严重的内皮损伤并影响微血管稳定性。但是,Res能够在Doxo处理组中增加外周细胞和平滑肌细胞的招募。我们还发现,Res比Doxo单独使用增加了VEGF的表达。通过H&E染色,Doxo处理的小鼠显示出内膜变化,影响上皮和基质组分。尽管如此,Res仍然恢复了子宫组织的结构。此外,我们还证明,Res的使用能够通过增加Doxo诱导的POF模型中的SOD表达来维护抗氧化防御。总之,Res在Doxo治疗前和治疗期间可能作为一种非侵入性和低成本的协议,用于保护女性癌症幸存者的卵巢功能。版权所有©2023 Elsevier B.V. 发布。
While oocytes and embryos cryopreservation can favor some patients with cancer-induced infertility to achieve pregnancy, the development of effective therapeutic strategies to preserve ovarian function during chemotherapy would be a significant advantage. The aim of the present study is to analyze whether Resveratrol treatment (Res) can preserve ovarian function from doxorubicin (Doxo)-induced gonadotoxicity using a mice model of premature ovarian failure. Res (7 and 15 mg/kg) increased the percentage of primary and antral follicles whilst decreasing the percentage of atretic follicles compared to Doxo alone. Res preserved the number of primordial follicles compared with those in the Doxo group but they did not change from those in the control group. Res treatment increased the number of AMH positive follicles compared to Doxo alone. Res increased proliferation index in follicular cells and reduced the DNA damage and apoptosis in preantral and early antral follicles compared to Doxo alone. Additionally, Doxo administration caused a severe endothelial damage and affected microvasculature stability in the ovary. However, Res was able to increase the recruitment of pericytes and smooth muscle cells in the Doxo-treated group. We also found that Res increased the expression of VEGF compared to Doxo alone. By H&E staining, Doxo-treated mice demonstrated endometrial alterations compared to controls, affecting both epithelial and stromal compartments. Nonetheless, Res restored the architecture of uterine tissue. Moreover, we also showed that Res administration is able to maintain antioxidant defenses through the increase of SOD expression in the Doxo-induced POF model. In conclusion, Res administration prior to and during Doxo treatment might serve as a noninvasive and low-cost protocol to preserve ovarian function in female cancer survivors.Copyright © 2023. Published by Elsevier B.V.