Affiliation:
1. Department of Obstetrics and Gynecology, Beijing Key laboratory of Reproductive Endocrinology and Assisted Reproductive Technology and Key Laboratory of Assisted Reproduction, Ministry of Education, Center for Reproductive Medicine, Peking University Third Hospital, Beijing, China
2. Department of Obstetrics and Gynecology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
Abstract
Abstract
Actinomycin D (ActD) has been considered as one of the most effective and safe chemotherapeutic medications for treating a number of cancers. Although ActD has been used in the treatment of gynecological tumors and pediatric tumors for more than 50 years, the toxic effects of ActD on mammalian oocytes remain unknown. In this study, the influence of ActD on mouse and human oocyte maturation and the possible mechanisms were investigated. Notably, ActD inhibited oocyte maturation and arrested oocytes at the metaphase I (MI) stage in a dose-dependent manner. In addition, ActD arrested oocyte maturation when the oocytes were treated at different successive stages, including the germinal vesicle (GV), germinal vesicle breakdown, and MI stages. In ActD-treated oocytes, disordered chromosome condensation and irregular spindle assembly occurred, resulting in incomplete chromosome segregation and oocytes arresting at the MI phase; these results possibly occurred because ActD triggered the formation of reactive oxygen species, resulting in DNA damage and decreased ATP in mouse GV oocytes. Besides, in vivo treatment with ActD also inhibited mouse oocyte maturation. Similar effects were seen in human oocytes. Collectively, our results indicated that ActD exposure disrupted oocyte maturation by increasing DNA damage, which is a finding that might help with optimizing future methods for female fertility preservation before undergoing chemotherapy.
Funder
National Key Research and Development Program of China
National Natural Science Foundation of China
Publisher
Oxford University Press (OUP)
Subject
Cell Biology,General Medicine,Reproductive Medicine
Cited by
3 articles.
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