Abstract:
Aflatoxin B1 (AFB1), usually seriously contaminates in grain and oil foods or feed, displayed significant acute and chronic toxic effects in human and animal populations. However, little is known about the transgenerational toxic effects induced by a maternal AFB1 intake at a lower dose on offspring. In our study, only parental wild-type Caenorhabditis elegans was exposed to AFB1 (0-8 μg/ml) and the following three filial generations were grown on AFB1-free NGM. Results showed that the toxic effects of AFB1 on the growth (body length) and reproduction (brood size, generation time and morphology of gonad arm) can be transmitted through generations. Moreover, the levels of MMP and ATP were irreversibly inhibited in the filial generations. By using RNomics and molecular biology techniques, we found that steroid biosynthesis, phagosome, valine/leucine/isoleucine biosynthesis and oxidative phosphorylation (p < 0.05) were the core signaling pathways to exert the transgenerational toxic effects on nematodes. Also, notably increased histone methylation level at H3K36me3 was observed in the first generation. Taken together, our study demonstrated that AFB1 has notable transgenerational toxic effects, which were resulted from the complex regulatory network of various miRNAs, mRNAs and epigenetic modification in C. elegans.
摘要:
黄曲霉毒素B1(AFB1),通常严重污染谷物和油类食品或饲料,在人类和动物种群中表现出明显的急性和慢性毒性作用。然而,关于母体低剂量摄入AFB1对后代引起的跨代毒性作用知之甚少。在我们的研究中,只有亲本野生型秀丽隐杆线虫暴露于AFB1(0-8μg/ml),随后的三代孝子在无AFB1的NGM上生长。结果表明,AFB1对生长(体长)和繁殖(育苗大小,性腺臂的生成时间和形态)可以通过世代传播。此外,子代的MMP和ATP水平受到不可逆的抑制。通过使用RNA组学和分子生物学技术,我们发现类固醇的生物合成,吞噬体,缬氨酸/亮氨酸/异亮氨酸生物合成和氧化磷酸化(p<0.05)是对线虫产生跨代毒性作用的核心信号通路。此外,在第一代中观察到H3K36me3组蛋白甲基化水平显著增加。一起来看,我们的研究表明,AFB1具有显著的跨代毒性作用,它们是由各种miRNA的复杂调控网络产生的,秀丽隐杆线虫的mRNA和表观遗传修饰。