Nucleoside reverse transcriptase inhibitor-induced rat oocyte dysfunction and low fertility mediated by autophagy.
Nucleoside reverse transcriptase inhibitor-induced rat oocyte dysfunction and low fertility mediated by autophagy.
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核苷逆转录酶抑制剂诱导大鼠卵母细胞功能障碍和自噬介导的低生育能力。
DOI：
10.18632/oncotarget.23243
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发表时间：
2018-01-09
期刊：
影响因子：
--
通讯作者：
Wang K
中科院分区：
文献类型：
--
作者：
Tang L;Yang S;Wang H;Gu H;Xia X;Feng Y;Yang Z;Zhao S;Su C;Su Z;Wang K
生育力低下是核苷类逆转录酶抑制剂（NRTI）最常见的副作用之一，而这一过程的分子机制在很大程度上尚不清楚。本研究旨在探讨自噬是否在NRTI诱导的雌性大鼠卵母细胞功能障碍和生育力低下中发挥作用。进行了体内和体外实验。对于体内实验，雌性成年Sprague-Dawley大鼠接受齐多夫定（AZT）和拉米夫定（3 TC）灌胃治疗3、6、9和12周;还设置了对照组。收集卵母细胞进行成熟评价、体外受精和线粒体功能测定以及细胞凋亡和自噬分析。对于体外实验，收集卵母细胞并分配到对照组、3-甲基腺嘌呤（3-MA，一种有效的自噬抑制剂）组、AZT组、AZT+3-MA组、3 TC组和3 TC +3-MA组。将卵母细胞与上述药物一起培养24、48和72 h，然后进行与体内研究相同的试验。结果显示，在体内和体外实验中，卵母细胞成熟相关标记物水平、卵母细胞卵裂率、囊胚形成率、线粒体DNA拷贝数和三磷酸腺苷水平以及细胞凋亡均呈时间依赖性显著降低，活性氧水平显著升高（所有P值均< 0.05）。这些变化，除了在卵母细胞成熟相关的标志物的变化，部分衰减3-MA。总之，我们证明了NRTIs可以导致大鼠卵母细胞功能障碍和生育力低下，这种损害至少部分是由自噬介导的。
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.
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影响因子：
14.9
作者：
Bess AS;Crocker TL;Ryde IT;Meyer JN
通讯作者：
Meyer JN
影响因子：
3.8
作者：
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通讯作者：
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3.8
作者：
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通讯作者：
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影响因子：
--
作者：
Ivanov AV;Valuev-Elliston VT;Ivanova ON;Kochetkov SN;Starodubova ES;Bartosch B;Isaguliants MG
通讯作者：
Isaguliants MG
影响因子：
3.7
作者：
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通讯作者：
Tavernarakis N