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丙烯腈暴露引发卵巢炎症,并通过诱导细胞凋亡导致卵母细胞质量下降,可能与线粒体功能障碍有关。

Acrylonitrile exposure triggers ovarian inflammation and decreases oocyte quality probably via mitochondrial dysfunction induced apoptosis in mice.

机构信息

Medical College, Guangxi University, Nanning, Guangxi, 530004, China.

Reproductive Medical Center of Nanning Second People's Hospital, Nanning, Guangxi, 530031, China.

出版信息

Chem Biol Interact. 2022 Jun 1;360:109934. doi: 10.1016/j.cbi.2022.109934. Epub 2022 Apr 13.

DOI:10.1016/j.cbi.2022.109934
PMID:35429547
Abstract

Acrylonitrile is an organic chemical synthetic monomer that is widely used in food packaging and manufacturing. Animal studies have reported that acrylonitrile is carcinogenic and toxic, but the effects on the female reproductive function in mammals are unknown. In the present study, we report that acrylonitrile treatment affects ovarian homeostasis in mice, resulting in impaired follicular development. Follicles in acrylonitrile-exposed mice exhibited high levels of inflammation and apoptosis, and acrylonitrile treatment interfered with oocyte development. Transcriptomics analysis showed that acrylonitrile altered the expression of oocyte genes related to apoptosis, oxidative stress, endoplasmic reticulum stress, and autophagy. Further molecular tests revealed that acrylonitrile induced early apoptosis, DNA damage, elevated levels of reactive oxygen species, endoplasmic reticulum abnormalities, and lysosomal aggregation. We also observed disruption of mitochondrial structure and distribution and depolarization of membrane potential. Finally, acrylonitrile treatment in female mice decreased the number and weight of offspring. Altogether, these findings suggest that acrylonitrile impairs the stability of the ovarian internal environment, which in turn affects oocyte development and reduces the number of offspring.

摘要

丙烯腈是一种有机化学合成单体,广泛应用于食品包装和制造。动物研究报告称丙烯腈具有致癌性和毒性,但对哺乳动物雌性生殖功能的影响尚不清楚。在本研究中,我们报告丙烯腈处理会影响小鼠的卵巢内稳态,导致卵泡发育受损。暴露于丙烯腈的小鼠卵泡表现出高水平的炎症和细胞凋亡,并且丙烯腈处理干扰了卵母细胞的发育。转录组学分析表明,丙烯腈改变了与细胞凋亡、氧化应激、内质网应激和自噬相关的卵母细胞基因的表达。进一步的分子测试表明,丙烯腈诱导早期细胞凋亡、DNA 损伤、活性氧水平升高、内质网异常和溶酶体聚集。我们还观察到线粒体结构和分布的破坏以及膜电位去极化。最后,雌性小鼠中丙烯腈的处理减少了后代的数量和体重。总之,这些发现表明丙烯腈破坏了卵巢内环境的稳定性,进而影响卵母细胞的发育并减少后代的数量。

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