Ochratoxin A exposure causes meiotic failure and oocyte deterioration in mice
Ochratoxin A exposure causes meiotic failure and oocyte deterioration in mice
复制标题
赭曲霉毒素 A 暴露导致小鼠减数分裂失败和卵母细胞退化
DOI：
10.1016/j.theriogenology.2019.11.005
复制
发表时间：
2020-05-01
期刊：
影响因子：
2.8
通讯作者：
Su, Jianmin
中科院分区：
文献类型：
--
作者：
Jia, Huiqun;Jia, Chenqi;Su, Jianmin
赭曲霉毒素A（OTA）是一种由真菌产生的真菌毒素，存在于各种食品和一些动物衍生产品中。这种霉菌毒素可对肾脏、肝脏、中枢神经和免疫系统造成有害影响。然而，关于OTA如何破坏哺乳动物卵母细胞质量的潜在机制尚未明确定义。在这项研究中，我们证明OTA通过损害卵母细胞减数分裂成熟来降低卵母细胞质量。我们发现，雌性小鼠腹腔注射（IP）1 mg/kg体重OTA治疗7天后，卵巢功能障碍，后代数量减少。我们还发现，OTA治疗在7.5 μ M为16小时，通过破坏纺锤体和染色体排列的第一极体挤出率下降。此外，OTA通过诱导减数分裂过程中活性氧的积累和抗氧化剂的消耗而引起氧化应激，从而导致卵母细胞凋亡。OTA预处理的卵母细胞线粒体损伤，能量供应不足，导致减数分裂失败。此外，表观遗传修饰也受到影响，显示小鼠卵母细胞中的5 mC、5 hmC、H3 K9 ac和H3 K9 me 3水平改变。总之，这些结果表明，OTA可以通过诱导氧化应激和表观遗传变化来降低卵母细胞的成熟和生育力。(C)2019爱思唯尔公司All rights reserved.
Ochratoxin A (OTA) is a mycotoxin produced by fungi and occurs naturally in various foodstuffs and some animal-derived products. This mycotoxin can cause deleterious effects on kidney, liver, central nervous, and immune system. However, potential mechanisms regarding how OTA disrupts the mammalian oocyte quality have not been clearly defined. In this study, we proved that OTA weakened oocyte quality by impairing oocyte meiotic maturation. We found that female mice treated with 1 mg/kg body weight OTA by intraperitoneal (IP) injection for 7 days displayed ovarian dysfunction and decreased offspring number. We also found that OTA treatment at 7.5 mu M for 16 h decreased the rate of first polar body extrusion by disrupting spindle and chromosome alignment. In addition, OTA caused oxidative stress by inducing the accumulation of reactive oxygen species and consumption of antioxidants during meiosis, consequently resulting in oocytes apoptosis. Mitochondrial damage and insufficient energy supply were also observed in OTA-pretreated oocytes, which led to the meiotic failure of oocyte. Moreover, the epigenetic modifications were also affected, showing with altered 5 mC, 5hmC, H3K9ac, and H3K9me3 levels in mice oocytes. In summary, these results showed that OTA could decrease oocyte maturation and fertility by inducing oxidative stress and epigenetic changes. (C) 2019 Elsevier Inc. All rights reserved.