Melatonin Reverses 10-Hydroxycamptothecin-Induced Apoptosis and Autophagy in Mouse Oocyte
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REPRODUCTIVE BIOLOGY: ORIGINAL ARTICLE
Melatonin Reverses 10-Hydroxycamptothecin-Induced Apoptosis and Autophagy in Mouse Oocyte Lining Wang 1 & Jingwen Zhang 1 & Chengtian Zhao 2 & Zhenzhen Jia 1 & Xizeng Feng 1 Received: 22 July 2020 / Accepted: 11 October 2020 # Society for Reproductive Investigation 2020
Abstract 10-Hydroxycamptothecin (HCPT) is a widely used anticancer drug that induces cytotoxicity by triggering the cell apoptotic pathway. Studies have shown that HCPT has harmful effects on normal cells, but whether HCPT affects the development of mouse oocytes in vitro has not been reported. First, this study investigated the development of oocytes exposed to 60 μM HCPT in vitro. In the HCPT-treated group, the first polar body extrusion (PBE) rate of oocytes decreased, spindle morphology was abnormal, DNA double-strand break, oxidative stress level increased, and mitochondrial distribution was abnormal. The apoptosis and autophagy levels of oocytes in the HCPT-treated group were detected by qRT-PCR and western blot. Compared with the control group, the expressions of key regulators of oocyte apoptosis (bax, caspase-3) and autophagy (lc3, beclin, ATG12) pathway were increased in the HCPT-treated group. HCPT treatment induced apoptosis and autophagy in oocytes. Melatonin (MT) can protect cell structure, prevent DNA damage, and reduce the content of peroxides. So we wondered whether MT could ameliorate the harmful effects of mouse oocytes induced by HCPT. Interestingly, the addition of 1 mM MT can protect oocytes from HCPT toxicity to some extent. Compared with the HCPT group, the addition of 1 mM MT increased the PBE ratio of oocytes, decreased ROS levels, and decreased spindle abnormalities and DNA breakage ratio. In summary, these results revealed that HCPT exhibited adverse effects on mouse oocyte maturation and quality, and MT administration alleviated the negative influence of HCPT. Keywords 10-Hydroxycamptothecin . Melatonin . Oocyte . Oxidative stress . Apoptosis
Introduction Reproductive toxicity caused by anticancer treatments such as invasive chemotherapy and radiation therapy is considered to be the most common pathological cause of loss of fertility in women [1–3]. It has been reported that chemotherapy drugs can increase the risk of ovarian follicles damage, premature ovarian failure, early menopause, and infertility [1, 4]. Lining Wang and Jingwen Zhang contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s43032-020-00359-4) contains supplementary material, which is available to authorized users. * Xizeng Feng [email protected] 1
College of Life Science, The Key Laboratory of Bioactive Materials, Ministry of Education, State Key Laboratory of Medicinal Chemical Biology, Nankai University, Weijin Road 94, Tianjin 300071, China
2
School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, China
Camptothecin (CPT) is a natural alkaloid extracted from Camptotheca accuminata a
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