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Exposure of preimplantation embryos to insulin alters expression of imprinted genes

机译:植入前胚胎暴露于胰岛素会改变印迹基因的表达

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Insulin promotes early embryonic development, but whether this action affects postimplantation fetal development and alters the expression of imprinted genes remain to be determined. This study analyzed the expression and methylation levels of the growth-related imprinted genes H19 and insulin-like growth factor 2 (Igf2) in fetuses exposed to insulin before implantation. We cultured 2-cell embryos in either 0 or 0.25 microg/ml insulin until the blastocyst stage and then transferred them into pseudopregnant recipient mice. The number of embryos developing to blastocysts after insulin exposure was 16.4% higher than that of the control, and the birth body weight of the insulin-exposed group was 17.8% higher than that of the control group. Real-time reverse transcription-polymerase chain reaction analysis revealed that exposure of preimplantation embryos to insulin increased the mRNA expression of both Igf2 and H19 in embryonic day (E) 14 fetuses. Bisulfite genomic sequencing demonstrated that the methylation level of the H19-Igf2 imprint control region was 19.3% lower in insulin-exposed E14 fetuses than in controls. The present study indicates that insulin exposure during the preimplantation stage alters the expression of imprinted genes and affects fetal development.
机译:胰岛素促进早期胚胎发育,但是这种作用是否影响植入后胎儿的发育并改变印迹基因的表达尚待确定。这项研究分析了植入前暴露于胰岛素的胎儿中与生长相关的印迹基因H19和胰岛素样生长因子2(Igf2)的表达和甲基化水平。我们在0或0.25 microg / ml胰岛素中培养2细胞胚胎直到胚泡期,然后将它们转移到假孕受体小鼠中。胰岛素暴露后发育为胚泡的胚胎数比对照组高16.4%,而胰岛素暴露组的出生体重比对照组高17.8%。实时逆转录-聚合酶链反应分析表明,植入前的胚胎暴露于胰岛素会增加14天胚胎日(E)胎儿的Igf2和H19的mRNA表达。亚硫酸氢盐基因组测序表明,暴露于胰岛素的E14胎儿的H19-Igf2印迹控制区域的甲基化水平比对照组低19.3%。本研究表明,在植入前阶段的胰岛素暴露会改变印迹基因的表达并影响胎儿发育。

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