The protective effects of resveratrol pretreatment in cyclophosphamide-induced rat ovarian injury: an vivo study

Abstract

Objectives

To explore whether resveratrol (Res) pretreatment could exert a protective effect on cyclophosphamide (Cy) induced ovarian toxicity in a rat model.

Methods

Twenty-four female 7-week old Sprague-Dawley rats were randomly divided into four groups: Con, administered with vehicle solutions; Cy, treated with Cy; Res + Cy, treated with Cy + Res combined; Res, treated with Res. After 21 d of treatments, the rats were euthanized and blood samples were collected to evaluate the levels of anti-Müllerian hormone (AMH). The Ovaries were processed for immunohistochemical and western blotting.

Results

Cy-treat caused the decrease of body weights and ovarian weight. AMH was lower in Cy group, whereas AMH levels were similar among other groups. Histomorphology showed a large number of primordial follicles were activated in Cy groups, whereas the primordial follicles were inhibited in the Res and Res + Cy groups. The expressions of Sirt1, Foxo3a were up-regulated and p53, Caspase-3, and Bax were down-regulated in Res + Cy and Res groups (p < .05).

Conclusions

Res can prevent the primordial follicle activation and decrease apoptosis induced by Cy. Res may be an effective protection for ovarian function during chemotherapy, which means a new nonsurgical application for protection of ovarian reserve.

白藜芦醇预处理对环磷酰胺致大鼠卵巢损伤的保护作用：体内研究 摘要

目的：探讨白藜芦醇（Res）预处理是否在环磷酰胺(Cy)作用的大鼠模型中诱导卵巢毒性有保护作用。

方法：将24只雌性7周龄 Sprague-Dawley大鼠随机分为四组：Con, 用赋形剂溶液处理；Cy, 用Cy处理；Res+Cy, 与Cy+Res结合处理；Res, 用 Res 处理。治疗21 d后处死大鼠并采集血样, 评估抗苗勒管激素 (AMH) 的水平。对卵巢进行免疫组化处理和蛋白质印迹。

结果： Cy处理组导致体重和卵巢质量下降。Cy组的AMH较低, 而其他组AMH水平相似。组织形态学显示大量原始Cy 组中的卵泡被激活, 而Res和Res+Cy组中的原始卵泡受到抑制。Sirt1、Foxo3a 表达上调, p53、Caspase-3 和 Bax在 Res+Cy组和 Res 组中表达下调（p <.05）。

结论：Res可抑制Cy诱导的原始卵泡活化, 减少细胞凋亡。Res可能是化疗期间对卵巢功能的有效保护, 这可能是一种新兴非手术用于保护卵巢储备功能的方法。

Keywords:

• Resveratrol
• cyclophosphamide
• ovary
• follicle
• toxicology
• apoptosis

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This research was supported by Hebei Provincial Science and Technology Department Fund for Medical Sciences [No. H2017206078] and Hebei Provincial Science and Technology Department Fund for Livelihood Science and Technology Special [No.192777106D].