Abstract
Chemotherapy-induced ovarian aging not only increases the risk for early menopause-related complications but also results in infertility in young female cancer survivors. Oogonial stem cells have the ability to generate new oocytes and thus provide new opportunities for treating ovarian aging and female infertility. Resveratrol (3,5,4′-trihydroxy-trans-stilbene) is a natural phenol derived from plants, that has been shown to have positive effects on longevity and redox flow in lipid metabolism and a preventive function against certain tumors. To evaluate whether resveratrol could promote the repair of oogonial stem cells damage in a busulfan/cyclophosphamide (Bu/Cy)-induced accelerated ovarian aging model, female mice were administered 30 and 100 mg/kg/d resveratrol through a gavage for 2 weeks. We demonstrated that resveratrol (30 mg/kg/d) relieved oogonial stem cells loss and showed an attenuating effect on Bu/Cy-induced oxidative apoptosis in mouse ovaries, which may be attributed to the attenuation of oxidative levels in ovaries. Additionally, we also showed that Res exerted a dose-dependent effect on oogonial stem cells and attenuated H2O2-induced cytotoxicity and oxidative stress injury by activating Nrf2 in vitro. Therefore, resveratrol could be of a potential therapeutic drug used to prevent chemotherapy-induced ovarian aging.
Highlights
Cancer is one of the most important global public health problems worldwide
Res was administered by gastrogavage at a low dosage of 30 mg/kg/d (30 Res group) and a high dosage of 100 mg/kg/d (100 Res group) to interfere with infertility mice treated with busulfan/cyclophosphamide (Bu/Cy)
After treatment with Res, especially in the 30 Res group, the morphology and weight of the ovaries were recovered compared with the chemotherapy group (Chemo group) (Figure 1A, 1B)
Summary
Thousands of young women are diagnosed with cancer every year and exposed to cytotoxic chemotherapy regimens and radiation, which have a substantial negative impact on reproduction [1]. These treatments may cause infertility and ovarian aging by inducing genomic damage and apoptotic death of oocytes [2]. Available fertility preservation strategies such as cryopreservation of gametes and ovarian tissue can help women achieve pregnancy. These strategies cannot reverse menopause or restore ovarian function [3]. Any drugs that preserve the function of ovaries during chemotherapy are urgently needed
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