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子宫内暴露于 2,3',4,4',5-五氯联苯对雄性后代生殖系统和精子表观遗传印记的影响。

Effects of intrauterine exposure to 2,3',4,4',5-pentachlorobiphenyl on the reproductive system and sperm epigenetic imprinting of male offspring.

机构信息

Shandong Provincial Key Laboratory of Animal Resistance Biology, College of Life Sciences, Shandong Normal University, Jinan, China.

State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.

出版信息

J Appl Toxicol. 2020 Oct;40(10):1396-1409. doi: 10.1002/jat.3992. Epub 2020 May 17.

DOI:10.1002/jat.3992
PMID:32418265
Abstract

Polychlorinated biphenyls (PCBs) are a class of persistent organic environmental pollutants with a total of 209 homologs. The homolog 2,3',4,4',5-pentachlorobiphenyl (PCB118) is one of the most important dioxin-like PCBs and is highly toxic. PCB118 can accumulate in human tissues, serum and breast milk, which leads to direct exposure of the fetus during development. In the present study, pregnant mice were exposed to 0, 20 and 100 μg/kg/day of PCB118 during the stage of fetal primordial germ cell migration. Compared with the control group, we found morphological alterations of the seminiferous tubules and a higher sperm deformity rate in the male offspring in the treatment groups. Furthermore, the methylation patterns in the treatment groups of the imprinted genes H19 and Gtl2 in the sperm were altered in the male offspring. We also characterized the disturbance of the expression levels of DNA methyltransferase 1 (Dnmt1), Dnmt3a, Dnmt3b, Dnmt3l, and Uhrf1. The results indicated that intrauterine exposure to low doses of PCB118 could significantly damage the reproductive health of the male offspring. Therefore, attention should be paid to the adverse effects of PCB118 exposure during pregnancy on the reproductive system of male offspring.

摘要

多氯联苯(PCBs)是一类持久性有机环境污染物,共有 209 种同系物。同系物 2,3',4,4',5-五氯联苯(PCB118)是最重要的二噁英类 PCBs 之一,具有高度毒性。PCB118 可以在人体组织、血清和母乳中积累,这导致胎儿在发育过程中直接暴露。在本研究中,在胎儿原始生殖细胞迁移阶段,怀孕小鼠每天暴露于 0、20 和 100μg/kg 的 PCB118 中。与对照组相比,我们在处理组的雄性后代中发现了精小管的形态改变和更高的精子畸形率。此外,处理组中雄性后代精子中印迹基因 H19 和 Gtl2 的甲基化模式发生改变。我们还描述了 DNA 甲基转移酶 1(Dnmt1)、Dnmt3a、Dnmt3b、Dnmt3l 和 Uhrf1 的表达水平受到干扰的情况。结果表明,宫内暴露于低剂量的 PCB118 可显著损害雄性后代的生殖健康。因此,应注意怀孕期间 PCB118 暴露对雄性后代生殖系统的不良影响。

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