Plasticizer Bis(2-ethylhexyl) Phthalate Causes Meiosis Defects and Decreases Fertilization Ability of Mouse Oocytes in Vivo
Plasticizer Bis(2-ethylhexyl) Phthalate Causes Meiosis Defects and Decreases Fertilization Ability of Mouse Oocytes in Vivo
复制标题
增塑剂邻苯二甲酸二（2-乙基己基）酯会导致减数分裂缺陷并降低小鼠卵母细胞体内的受精能力
DOI：
10.1021/acs.jafc.9b00121
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发表时间：
2019-03-27
影响因子：
6.1
通讯作者：
Su, Jianmin
中科院分区：
文献类型：
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作者：
Lu, Zhenzhen;Zhang, Chengtu;Su, Jianmin
邻苯二甲酸二（2-乙基己基）酯（DEHP）是聚氯乙烯（PVC）塑料中广泛使用的增塑剂。人类和动物广泛且持续地暴露于DEHP，特别是在饮食方面，这与生殖疾病有关。然而，DEHP暴露对体内卵母细胞的影响和潜在机制仍然不明确。在这项研究中，我们发现口服DEHP（40 μ g/kg体重/天，持续14天）显著降低了体内卵母细胞的成熟和受精。此外，DEHP引起氧化应激，增加活性氧的产生，促进早期凋亡，并导致小鼠卵母细胞的DNA损伤。此外，DEHP暴露导致小鼠卵母细胞线粒体损伤，ATP含量降低，肌动蛋白表达下调，纺锤体组装和染色体排列紊乱。此外，DEHP暴露显著损害了精子受体Juno在卵母细胞膜上的定位和蛋白水平。DNA甲基化水平，H3 K9 me 3和H3 K9 ac也在DEHP暴露的小鼠卵母细胞中改变。因此，我们的研究结果表明，DEHP暴露通过影响小鼠卵母细胞的细胞骨架动力学、氧化应激、早期凋亡、减数分裂纺锤体形态、线粒体、ATP含量、Juno表达、DNA损伤和表观遗传修饰，降低了小鼠卵母细胞的成熟和受精能力。
Bis(2-ethylhexyl) phthalate (DEHP) is a widely used plasticizer in polyvinyl chloride (PVC) plastics. Humans and animals are widely and continuously exposed to DEHP, especially with respect to diet, which is associated with reproductive diseases. Nevertheless, the effects and underlying mechanisms of DEHP exposure on oocytes in vivo remain ambiguous. In this study, we found that oral administration of DEHP (40 mu g/kg body weight per day for 14 days) markedly reduced the maturation and fertilization of oocytes in vivo. In addition, DEHP caused oxidative stress, increased reactive oxygen species generation, promoted early apoptosis, and resulted in DNA damage in mouse oocytes. Moreover, DEHP exposure caused mitochondrial damage, reduced ATP content, down-regulated actin expression, and disturbed the spindle assembly and chromosome alignment in mouse oocytes. Furthermore, DEHP exposure remarkably impaired the localization and protein level of Juno, the sperm receptor on the membrane of oocytes. The levels of DNA methylation, H3K9me3, and H3K9ac were also altered in the DEHP-exposed mouse oocytes. Thus, our results indicated that DEHP exposure reduced the maturation and fertilization capabilities of mouse oocytes by affecting cytoskeletal dynamics, oxidative stress, early apoptosis, meiotic spindle morphology, mitochondria, ATP content, Juno expression, DNA damage, and epigenetic modifications in mouse oocytes.