机构：[1]Department of Reproduction and Genetics, The First Affiliated Hospital of Kunming Medical University, Kunming, 650032, Yunnan Province, China外科科室医技科室生殖遗传科医学影像中心CT室昆明医科大学附属第一医院[2]Department of Reproductive Medicine, The First People’s Hospital of Yunnan Province, Kunming, 650032, Yunnan Province, China云南省第一人民医院[3]Department of Pharmacy, The First People’s Hospital of Yunnan Province, Kunming, 650032, Yunnan Province, China云南省第一人民医院[4]Yunnan Institute of Digestive Disease, The First Affiliated Hospital of Kunming Medical University, Kunming, 650032, Yunnan Province, China昆明医科大学附属第一医院省级研究所云南省消化疾病研究所[5]Department of Life Science, Kunming University of Science and Technology, Kunming, 650093, Yunnan Province, China
Low fertility is one of the most common side effects caused by nucleoside reverse transcriptase inhibitors (NRTIs), whereas the molecular mechanism underlying this process were largely unclear. This study was conducted to investigate whether autophagy plays a role in NRTIs-induced oocyte dysfunction and low fertility in female rat. Both in vivo and in vitro experiments were conducted. For the in vivo experiment, female adult Sprague-Dawley rats were subjected to zidovudine (AZT) and lamivudine (3TC) intragastric treatment for 3, 6, 9, and 12 weeks; a control was also set. Oocytes were collected for maturation evaluation, in vitro fertilization and mitochondrial function assays, and apoptosis and autophagy analysis. For the in vitro experiment, oocytes were collected and assigned to the control, 3-methyladenine (3-MA, an effective autophagy inhibitor), AZT, AZT+3-MA, 3TC, and 3TC+3-MA groups. The oocytes were cultured with the abovementioned drugs for 24, 48, and 72 h and then, subjected to the same assays as in the in vivo study. The results showed a significant time-dependent decrease in oocyte maturation-related maker levels, oocyte cleavage rate, blastocyst formation rate, mitochondrial DNA copy number and adenosine triphosphate level, and apoptosis, and a significant increase in the reactive oxygen species levels (all P-values < 0.05), in both the in vivo and the in vitro experiments. These changes, except for the changes in the oocyte maturation-related markers, were partially attenuated by 3-MA. In conclusion, we demonstrated that NRTIs can cause rat oocyte dysfunction and low fertility, and this damage was, at least partially, mediated by autophagy.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81260510, 81660094]; Major project of Yunnan Provincial Bureau of Education [ZD2015010]; Key Science and Technology planning Project of Yunnan Provincial Science and Technology Department [2016FC005]; Key Science and Technology planning Project of Kunming Science and Technology Bureau
基金编号：8126051081660094ZD20150102016FC005
语种：
外文
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第一作者：
第一作者机构：[1]Department of Reproduction and Genetics, The First Affiliated Hospital of Kunming Medical University, Kunming, 650032, Yunnan Province, China[2]Department of Reproductive Medicine, The First People’s Hospital of Yunnan Province, Kunming, 650032, Yunnan Province, China
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推荐引用方式(GB/T 7714)：
Tang Li,Yang Shengfu,Wang Huawei,et al.Nucleoside reverse transcriptase inhibitor-induced rat oocyte dysfunction and low fertility mediated by autophagy[J].ONCOTARGET.2018,9(3):3895-3907.doi:10.18632/oncotarget.23243.
APA：
Tang, Li,Yang, Shengfu,Wang, Huawei,Gu, Hai,Xia, Xueshan...&Wang, Kunhua.(2018).Nucleoside reverse transcriptase inhibitor-induced rat oocyte dysfunction and low fertility mediated by autophagy.ONCOTARGET,9,(3)
MLA：
Tang, Li,et al."Nucleoside reverse transcriptase inhibitor-induced rat oocyte dysfunction and low fertility mediated by autophagy".ONCOTARGET 9..3(2018):3895-3907
