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褪黑素可保护体外成熟的猪卵母细胞免受黄曲霉毒素 B1 的毒性影响。

Melatonin protects in vitro matured porcine oocytes from toxicity of Aflatoxin B1.

机构信息

Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, China.

Assisted Reproductive Centre of the Department of Gynaecology and Obstetrics, PLA Naval General Hospital, Beijing, China.

出版信息

J Pineal Res. 2019 May;66(4):e12543. doi: 10.1111/jpi.12543. Epub 2019 Mar 26.

Abstract

Aflatoxin B1 (AFB1) is a major food and feed contaminant that threaten public health. Previous studies indicate that AFB1 exposure disrupted oocyte maturation. However, an effective and feasible method is unavailable for protecting oocytes against toxicity of AFB1. In the present study, using in vitro matured porcine oocytes and parthenogenetic embryos as model, we confirmed that AFB1 exposure during in vitro oocyte maturation (IVM) significantly impaired both nuclear and cytoplasmic maturation in a dose- and time-dependent manner. The different concentrations of melatonin were also tested for their protective effects on oocytes against the AFB1-induced toxicity. Our results showed that supplementation of a relative high concentration of melatonin (10 mol/L) during IVM efficiently reversed the impaired development rate and blastocyst quality, to the levels comparable to those of the control group. Further analysis indicated that melatonin application efficiently alleviated reactive oxygen species accumulation and initiation of apoptosis induced by AFB1 exposure. In addition, disrupted GSH/GPX system, as well as inhibited mitochondrial DNA (mtDNA) replication and mitochondrial biogenesis in AFB1-treated oocytes, can be notably reversed by melatonin application. Furthermore, cumulus cells may be important in mediating the toxicity of AFB1 to oocytes, and the metabolism of AFB1 in cumulus cells can be depressed by melatonin. To the best of our knowledge, this is the first report to confirm that melatonin application can efficiently protect oocytes from AFB1-induced toxicity. Our study provides a promising and practical strategy for alleviating or reversing AFB1-induced female reproductive toxicity in both clinical treatment and domestic reproductive management.

摘要

黄曲霉毒素 B1(AFB1)是一种主要的食品和饲料污染物,威胁着公众健康。先前的研究表明,AFB1 暴露会破坏卵母细胞的成熟。然而,目前还没有有效的可行方法来保护卵母细胞免受 AFB1 的毒性影响。在本研究中,我们使用体外成熟的猪卵母细胞和孤雌胚胎作为模型,证实了 AFB1 在体外卵母细胞成熟(IVM)期间的暴露以剂量和时间依赖的方式显著损害了核和细胞质成熟。还测试了不同浓度的褪黑素对卵母细胞对抗 AFB1 毒性的保护作用。我们的结果表明,在 IVM 期间补充相对高浓度的褪黑素(10 mol/L)可以有效地逆转受损的发育率和囊胚质量,使其达到与对照组相当的水平。进一步的分析表明,褪黑素的应用可以有效地减轻 AFB1 暴露引起的活性氧积累和凋亡的启动。此外,AFB1 处理的卵母细胞中受损的 GSH/GPX 系统以及抑制的线粒体 DNA(mtDNA)复制和线粒体生物发生可以通过褪黑素的应用得到明显逆转。此外,卵丘细胞可能在介导 AFB1 对卵母细胞的毒性方面起着重要作用,并且褪黑素可以抑制卵丘细胞中 AFB1 的代谢。据我们所知,这是第一项证实褪黑素应用可以有效保护卵母细胞免受 AFB1 诱导的毒性的报告。我们的研究为缓解或逆转 AFB1 引起的女性生殖毒性提供了一种有前途的实用策略,无论是在临床治疗还是家庭生殖管理中。

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