Isoflurane impairs oogenesis through germ cell apoptosis in C. elegans

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作者
Tao Zhang
Cheng Ni
Cheng Li
Pan Lu
Dan Chen
Yuanlin Dong
Johnathan R. Whetstine
Yiying Zhang
Zhongcong Xie
机构
[1] Tenth People’s Hospital of Tongji University,Department of Anesthesiology
[2] Chinese Academy of Medical Sciences and Peking Union Medical College,Department of Anesthesiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital
[3] Tongji University,Department of Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain
[4] Massachusetts General Hospital and Harvard Medical School,Like Intelligence, Shanghai Fourth People’s Hospital, School of Medicine
[5] Xi’an Jiaotong University Second Affiliated Hospital,Geriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine
[6] Fox Chase Cancer Center,Department of Anesthesiology
[7] Fox Chase Cancer Center,Cancer Epigenetics Institute
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摘要
Anesthetic isoflurane has been reported to induce toxicity. However, the effects of isoflurane on fecundity remain largely unknown. We established a system in C. elegans to investigate the effects of isoflurane on oogenesis. Synchronized L4 stage C. elegans were treated with 7% isoflurane for 4 h. Dead cells, ROS, embryos, and unfertilized eggs laid by hermaphrodites were measured by fluorescence imaging and counting. The C. elegans with losses of ced-3, cep-1, abl-1, male C. elegans, and oxidative stress inhibitor N-acetyl-cysteine were used in the interaction studies. We found that isoflurane decreased the numbers of embryos and unfertilized eggs and increased the levels of dead cells and ROS in C. elegans. The isoflurane-induced impairment of oogenesis was associated with abl-1, ced-3, but not cep-1. N-acetyl-cysteine attenuated the isoflurane-induced impairment of oogenesis in C. elegans. Mating with male C. elegans did not attenuate the isoflurane-induced changes in oogenesis. These findings suggest that isoflurane may impair oogenesis through abl-1- and ced-3-associated, but not cep-1-associated, germ cell apoptosis and oxidative stress, pending further investigation. These studies will promote more research to determine the potential effects of anesthesia on fecundity.
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