Sodium nitrite negatively affects reproductive ability and offspring survival in female mice
Sodium nitrite negatively affects reproductive ability and offspring survival in female mice
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亚硝酸钠对雌性小鼠的生殖能力和后代存活率产生负面影响
DOI：
10.1016/j.tox.2019.152284
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发表时间：
2019-11-01
期刊：
影响因子：
4.5
通讯作者：
Liang, Cheng-Guang
中科院分区：
文献类型：
--
作者：
Ge, Lei;Han, Zhe;Liang, Cheng-Guang
亚硝酸钠（NaNO 2）是一种工业化学品，经常用作食品添加剂，以防止肉毒杆菌中毒并提高光泽度，例如腌制肉类。此外，在一些地区，水源NaNO 2浓度超过标准监管水平。过量摄入NaNO 2是否对女性生育能力和胎儿发育有毒性影响尚不清楚。在这项研究中，我们通过灌胃给予ICR小鼠对照盐水、低剂量NaNO 2（60 mg/kg/天）或高剂量NaNO 2（120 mg/kg/天），持续21天。然后，我们评估了卵母细胞形态，纺锤体染色体动力学，线粒体分布，ATP含量，凋亡细胞数量，DNA损伤水平，组蛋白修饰，活性氧（ROS）水平和后代存活率。结果表明，NaNO 2处理减少卵母细胞数量，破坏极体的排出，并增加卵母细胞的透明膜厚度。此外，NaNO 2破坏了MII纺锤体的完整性，导致线粒体分布异常，ATP含量降低，ROS和H3 K4 me 2水平升高。此外，在NaNO 2处理的小鼠中，处于细胞凋亡早期阶段的卵母细胞数量和DNA损伤水平增加沿着后代数量和存活率下降。我们证明了NaNO 2对小鼠雌性生殖能力的负面影响。
Sodium nitrite (NaNO2) is an industrial chemical that is frequently used as a food additive to prevent botulism and enhance glossiness, such as curing meat. In addition, in some regions, water source NaNO2 concentrations exceed standard regulatory levels. Whether the excessive intake of NaNO2 has toxic effects on female fertility and fetal development remain unknown. In this study, we administered ICR mice control saline, low-dose NaNO2 (60 mg/kg/day), or high-dose NaNO2 (120 mg/kg/day) by intragastric gavage for 21 days. We then assessed oocyte morphology, spindle-chromosome dynamics, mitochondrial distribution, ATP content, apoptotic cell numbers, DNA damage levels, histone modifications, reactive oxygen species (ROS) levels, and offspring survival. Results showed that NaNO2 treatment decreased oocyte number, impaired polar body extrusion, and increased zona pellucida thickness in oocytes. Furthermore, NaNO2 disrupted MII spindle integrity, caused abnormal mitochondrial distribution, decreased ATP content, and increased levels of ROS and H3K4me2. Moreover, the number of oocytes in early stages of apoptosis and with levels of DNA damage increased in NaNO2-treated mice along with decreased offspring numbers and survival rates. We demonstrated the negative effects of NaNO2 on female reproductive abilities in mice.