Background

Cyclophosphamide (CTX), which has been used to treat common female cancers for several years, often causes ovarian damage, early menopause and infertility. However, strategies for the effective prevention and treatment of CTX-induced ovarian damage are still lacking. Epigallocatechin gallate (EGCG) and theaflavins (TFs), key molecules derived from green tea or black tea, have been shown to exert preventive effects on many ageing-related diseases.

Purpose

We aimed to explore the potential preventive and protective effects of EGCG and TFs on CTX-induced ovarian damage and compare the two compounds.

Study Design

Six-week-old female mice were administered a low or high dose of EGCG or TFs. The low dose was equivalent to the average daily amount of tea consumed by a drinker.

Methods

We determined the oestrous cycle and serum hormone levels to evaluate ovarian endocrine function, and we performed mating tests for reproductivity. We also assessed the follicle count and AMH level to evaluate ovarian reserve, and we performed Masson's trichrome and Sirius red staining to evaluate ovarian fibrosis. We conducted γ-H2AX and TUNEL analyses to evaluate DNA damage, and we also measured the relevant indicators of oxidative stress and follicular activation, including NRF2, HO-1, SOD2, AKT, mTOR and RPS6.

Results

EGCG and TFs treatment independently improved the ovarian endocrine function and reproductivity of mice that were administered CTX. EGCG and TFs also increased the ovarian reserve of these animals. Furthermore, EGCG and TFs alleviated oxidation-induced damage to ovarian DNA in mice by activating the NRF2/HO-1 and SOD2 pathways and reducing the apoptosis of growing follicles. At the same time, EGCG and TFs reduced the overactivation of primordial follicles by inhibiting the AKT/mTOR/RPS6 pathway.

Conclusion

The present study showed that EGCG and TFs independently improved ovarian function in mice with CTX-induced ovarian damage, thereby providing useful information for designing a potential clinical strategy that will protect against chemotherapy-induced ovarian damage.

中文翻译：

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表没食子儿茶素没食子酸酯和茶黄素通过抑制原始卵泡过度激活和卵泡闭锁独立减轻环磷酰胺诱导的卵巢损伤

背景

多年来一直用于治疗常见女性癌症的环磷酰胺 (CTX) 经常会导致卵巢损伤、更年期提前和不孕症。然而，仍然缺乏有效预防和治疗 CTX 引起的卵巢损伤的策略。表没食子儿茶素没食子酸酯 (EGCG) 和茶黄素 (TFs) 是源自绿茶或红茶的关键分子，已被证明对许多与衰老相关的疾病具有预防作用。

目的

我们旨在探索 EGCG 和 TFs 对 CTX 诱导的卵巢损伤的潜在预防和保护作用，并比较这两种化合物。

学习规划

六周大的雌性小鼠被给予低剂量或高剂量的 EGCG 或 TF。低剂量相当于饮用者每天平均饮用的茶量。

方法

我们确定了发情周期和血清激素水平以评估卵巢内分泌功能，并进行了生殖能力的交配测试。我们还评估了卵泡计数和 AMH 水平以评估卵巢储备，并且我们进行了马森三色和天狼星红染色以评估卵巢纤维化。我们进行了 γ-H2AX 和 TUNEL 分析以评估 DNA 损伤，我们还测量了氧化应激和卵泡激活的相关指标，包括 NRF2、HO-1、SOD2、AKT、mTOR 和 RPS6。

结果

EGCG 和 TFs 治疗独立地改善了给予 CTX 的小鼠的卵巢内分泌功能和生殖能力。EGCG 和 TFs 也增加了这些动物的卵巢储备。此外，EGCG 和 TFs 通过激活 NRF2/HO-1 和 SOD2 通路并减少生长中的卵泡的凋亡，减轻了氧化诱导的小鼠卵巢 DNA 损伤。同时，EGCG和TFs通过抑制AKT/mTOR/RPS6通路减少原始卵泡的过度激活。

结论

本研究表明，EGCG 和 TFs 独立改善了 CTX 诱导的卵巢损伤小鼠的卵巢功能，从而为设计一种潜在的临床策略提供了有用的信息，以防止化疗诱导的卵巢损伤。