Effects of 2,3′,4,4′5-pentachlorobiphenyl exposure during pregnancy on epigenetic imprinting and maturation of offspring's oocytes in mice
Effects of 2,3′,4,4′5-pentachlorobiphenyl exposure during pregnancy on epigenetic imprinting and maturation of offspring's oocytes in mice
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妊娠期间接触 2,3–2,4,4–5–五氯联苯对小鼠后代卵母细胞表观遗传印记和成熟的影响
DOI：
10.1007/s00204-019-02529-z
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发表时间：
2019-09-01
影响因子：
6.1
通讯作者：
Liu, Shu-Zhen
中科院分区：
文献类型：
--
作者：
He, Qi-Long;Wei, Xu-Yu;Liu, Shu-Zhen
多氯联苯（PCBs）是一类广泛存在于环境中的有机污染物。2，3 '，4，4'，5-五氯联苯（PCB 118）是一种重要的二恶英类多氯联苯化合物，具有很强的毒性。PCB 118可在哺乳动物的脂肪组织、血清和乳汁中积累，在卵泡液中高度富集。在这项研究中，怀孕小鼠在怀孕期间胎儿原始生殖细胞迁移阶段分别接触0、20和100微克/千克/天的多氯联苯118。在子代中检测印记基因H19、Snrpn、Peg 3和Igf 2 r的甲基化模式以及Dnmt 1、3a、3b和3l、Uhrf 1、Tet 2和Tet 3在完全发育的胚泡卵母细胞中的表达水平。计算体外成熟率、体外受精率、卵母细胞纺锤体率和染色体异常率。结果表明，PCB 118产前暴露改变了部分印迹基因差异甲基化区域的DNA甲基化状态，Dnmt 1、3a和3l、Uhrf 1和Tet 3的表达水平也发生了变化。此外，PCB 118以剂量依赖的方式干扰子代小鼠卵母细胞的成熟过程。因此，应关注孕期摄入PCB 118污染的膳食对子代生殖健康的潜在影响。
Polychlorinated biphenyls (PCBs) are a class of organic pollutants that have been widely found in the environment. The chemical 2,3 ',4,4 ' 5-pentachlorobiphenyl (PCB118) is an important dioxin-like PCB compound with strong toxicity. PCB118 can accumulate in adipose tissue, serum and milk in mammals, and it is highly enriched in the follicular fluid. In this study, pregnant mice were exposed to 0, 20 and 100 mu g/kg/day of PCB118 during pregnancy at the fetal primordial germ cell migration stage. The methylation patterns of the imprinted genes H19, Snrpn, Peg3 and Igf2r as well as the expression levels of Dnmt1, 3a, 3b and 3l, Uhrf1, Tet2 and Tet3 in fully grown germinal vesicle oocytes were measured in offspring. The rates of in vitro maturation, in vitro fertilization, oocyte spindle and chromosomal abnormalities were also calculated. The results showed that prenatal exposure to PCB118 altered the DNA methylation status of differentially methylated regions in some imprinted genes, and the expression levels of Dnmt1, 3a, and 3l, Uhrf1 and Tet3 were also changed. In addition, PCB118 disturbed the maturation process of progeny mouse oocytes in a dose-dependent manner. Therefore, attention should be paid to the potential impacts of PCB118-contaminated dietary intake during pregnancy on the offspring's reproductive health.