Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan, Hubei, China.
Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan, Hubei, China; Department of Pediatrics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Phytomedicine. 2021 Nov;92:153752. doi: 10.1016/j.phymed.2021.153752. Epub 2021 Sep 14.
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.
We aimed to explore the potential preventive and protective effects of EGCG and TFs on CTX-induced ovarian damage and compare the two compounds.
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.
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.
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.
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.
环磷酰胺（CTX）已被用于治疗多种常见女性癌症多年，但其常导致卵巢损伤、早绝经和不孕。然而，针对 CTX 诱导的卵巢损伤的有效防治策略仍十分缺乏。表没食子儿茶素没食子酸酯（EGCG）和茶黄素（TFs）是绿茶或红茶中的关键分子，已被证明对许多与衰老相关的疾病具有防治作用。
我们旨在探讨 EGCG 和 TFs 对 CTX 诱导的卵巢损伤的潜在防治作用，并比较这两种化合物。
6 周龄雌性小鼠给予低剂量或高剂量的 EGCG 或 TFs。低剂量相当于饮茶者的平均日摄入量。
我们通过发情周期和血清激素水平评估卵巢内分泌功能，并进行交配试验评估生殖能力。我们还通过卵泡计数和 AMH 水平评估卵巢储备功能，并进行 Masson 三色和 Sirius 红染色评估卵巢纤维化。我们通过 γ-H2AX 和 TUNEL 分析评估 DNA 损伤，并测量相关的氧化应激和卵泡激活指标，包括 NRF2、HO-1、SOD2、AKT、mTOR 和 RPS6。
EGCG 和 TFs 治疗可独立改善 CTX 处理小鼠的卵巢内分泌功能和生殖能力。EGCG 和 TFs 还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 途径以及减少生长卵泡的凋亡，缓解了 CTX 处理小鼠卵巢 DNA 的氧化损伤。同时，EGCG 和 TFs 通过抑制 AKT/mTOR/RPS6 途径减少原始卵泡的过度激活。
本研究表明，EGCG 和 TFs 可独立改善 CTX 诱导的卵巢损伤小鼠的卵巢功能，为设计一种潜在的临床策略提供了有用的信息，以防止化疗引起的卵巢损伤。
