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氟化钠会干扰NNAT的DNA甲基化,并通过损害猪卵母细胞中的葡萄糖转运来降低卵母细胞质量。

Sodium fluoride disturbs DNA methylation of NNAT and declines oocyte quality by impairing glucose transport in porcine oocytes.

作者信息

Liu Xiaoyan, Nie Zheng-Wen, Gao Ying-Ying, Chen Li, Yin Shu-Yuan, Zhang Xia, Hao Cuifang, Miao Yi-Liang

机构信息

Institute of Stem Cell and Regenerative Biology, College of Animal Science and Technology & College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China.

Reproductive Medicine Centre, Affiliated Hospital of Qingdao Medical University, Yuhuangding Hospital of Yantai, Yantai, Shandong, China.

出版信息

Environ Mol Mutagen. 2018 Apr;59(3):223-233. doi: 10.1002/em.22165. Epub 2017 Dec 29.

DOI:10.1002/em.22165
PMID:29285797
Abstract

Sodium fluoride (NaF) is used as a medicine to prevent tooth decay; however, excessive NaF could cause a pathological damage to the health. Recent studies showed that NaF impaired mouse oocyte maturation, included of abnormal spindle configuration, actin cap formation, cortical granule-free domain formation, and the following development after fertilization. However, few studies used large animals as models to study the toxicology of NaF on oocytes maturation. We proposed a hypothesis that NaF would affect the nuclear and cytoplasmic maturation of porcine oocytes and DNA methylation pattern of imprinted genes in oocytes. Our results showed that NaF affected cumulus expansion, polar body emission, spindle morphology, cortical granule distribution, early apoptosis, and the following development after parthenogenetic activation during porcine oocyte maturation. Moreover, NaF increased the DNA methylation of NNAT and decreased its expression, which disturbed the glucose transport in oocytes. These results suggest that NaF impairs the porcine oocytes maturation epigenetically, which provides a new toxicological mechanism of NaF on the oocyte maturation. Environ. Mol. Mutagen. 59:223-233, 2018. © 2017 Wiley Periodicals, Inc.

摘要

氟化钠(NaF)被用作预防龋齿的药物;然而,过量的NaF可能会对健康造成病理损害。最近的研究表明,NaF会损害小鼠卵母细胞成熟,包括纺锤体构型异常、肌动蛋白帽形成、无皮质颗粒区形成以及受精后的后续发育。然而,很少有研究使用大型动物作为模型来研究NaF对卵母细胞成熟的毒理学。我们提出了一个假设,即NaF会影响猪卵母细胞的核成熟和胞质成熟以及卵母细胞中印迹基因的DNA甲基化模式。我们的结果表明,NaF在猪卵母细胞成熟过程中影响卵丘扩展、极体排放、纺锤体形态、皮质颗粒分布、早期凋亡以及孤雌激活后的后续发育。此外,NaF增加了NNAT的DNA甲基化并降低了其表达,这扰乱了卵母细胞中的葡萄糖转运。这些结果表明,NaF通过表观遗传方式损害猪卵母细胞成熟,这为NaF对卵母细胞成熟的毒理学提供了一种新机制。《环境与分子突变》59:223 - 233,2018年。© 2017威利期刊公司

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