Oral administration of olaquindox negatively affects oocytes quality and reproductive ability in female mice
Oral administration of olaquindox negatively affects oocytes quality and reproductive ability in female mice
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口服喹乙醇会对雌性小鼠的卵母细胞质量和生殖能力产生负面影响
DOI：
10.1016/j.ecoenv.2020.110826
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发表时间：
2020
影响因子：
6.8
通讯作者：
Cheng-Guang Liang
中科院分区：
文献类型：
--
作者：
Yu-Qing Gao;Lei Ge;Zhe Han;Xin Hao;Mei-Ling Zhang;Xiao-Jie Zhang;Cheng-Jie Zhou;De-Jian Zhang;Cheng-Guang Liang
喹乙醇（奥拉）作为一种有效的饲料添加剂，在畜禽生产中得到了广泛的应用。然而，奥拉对哺乳动物卵母细胞质量和胎儿发育是否有负面影响尚不清楚。本研究通过ICR小鼠连续45天灌胃水、低剂量奥拉（5 mg/kg/天）或高剂量奥拉（60 mg/kg/天），检测奥拉的毒性作用。结果表明，高剂量奥拉灌胃对仔鼠的出生和生长发育有严重影响。高剂量奥拉明显损害卵母细胞成熟和早期胚胎发育，表现为胚泡破裂、第一极体排出和囊胚形成的百分比降低。与此同时，卵巢和卵母细胞的氧化应激水平也有所升高，表现为ROS、MDA、H2 O2、NO水平升高，GSH、SOD、CAT、GSH-Px和GSH-Rd水平降低。高剂量奥拉灌胃后，线粒体分布异常，纺锤体组装缺陷，H3 K4 me 2/H3 K9 me 3水平异常，DNA双链断裂增加，早期凋亡率增加。综上所述，我们的研究结果首次表明，高剂量奥拉灌胃导致雌性生育力低下，这意味着应考虑限制使用奥拉作为饲料添加剂。
As an effective feed additive in the livestock industry, olaquindox (OLA) has been widely used in domestic animal production. However, it is unclear whether OLA has negative effects on mammalian oocyte quality andfetal development. In this study, toxic effects of OLA were tested by intragastric gavage ICR mice with water, low-dose OLA (5 mg/kg/day), or high-dose OLA (60 mg/kg/day) for continuous 45 days. Results showed that high-dose OLA gavage severely affected the offspring birth and growth. Significantly, high-dose OLA impaired oocyte maturation and early embryo development, indicated by the decreased percentage of germinal vesicle breakdown, first polar body extrusion and blastocyst formation. Meanwhile, oxidative stress levels were increased in oocytes or ovaries, indexed by the increased levels of ROS, MDA, H2O2, NO, and decreased levels of GSH, SOD, CAT, GSH-Px and GSH-Rd. Furthermore, aberrant mitochondria distribution, defective spindle assembly, abnormal H3K4me2/H3K9me3 levels, increased DNA double-strand breaks and early apoptosis rate,.were observed after high-dose OLA gavage. Taken together, our results for the first time illustrated that highdose OLA gavage led to sub-fertility of females, which means that restricted utilization of OLA as feed additive should be considered.