Loss of imprinting of the Igf2-H19 ICR1 enhances placental endocrine capacity via sex-specific alterations in signalling pathways in the mouse.
Loss of imprinting of the Igf2-H19 ICR1 enhances placental endocrine capacity via sex-specific alterations in signalling pathways in the mouse.
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DOI：
10.1242/dev.199811
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发表时间：
2022-01-01
期刊：
影响因子：
--
通讯作者：
Sferruzzi-Perri AN
中科院分区：
文献类型：
--
作者：
Aykroyd BRL;Tunster SJ;Sferruzzi-Perri AN
印迹控制区（ICR 1）控制Igf 2和H19基因的表达，在父母的起源特异性的方式。Igf 2-H19位点的适当表达是胎儿正常发育的基础，但ICR 1在胎盘产生促进母体营养分配给胎儿的激素中的重要性尚不清楚。为了解决这个问题，我们使用了一种新的小鼠模型来选择性地删除小鼠胎盘内分泌结合区（Jz）中的ICR 1（Jz-Δ ICR 1）。Jz-Δ ICR 1小鼠在Jz中特异性地表现出Igf 2表达增加和H19表达减少。这是伴随着一个扩展的Jz内分泌细胞类型，由于增强的增殖率和增加表达的妊娠特异性糖蛋白23在两个胎儿性别的胎盘。然而，胎盘内分泌表型的变化与Igf 2受体丰度和下游信号通路（Pi 3 k-Akt和Mapk）的性二态性改变有关。Jz-Δ ICR 1对H19嵌入的miR-675的靶点表达或胎儿体重没有影响。我们的研究结果表明，ICR 1控制胎盘内分泌能力，通过性别依赖性的信号转导的变化。总结：在小鼠中，在Igf 2-H19处的印记ICR 1通过Pi 3 k-Akt和Mapk信号传导中的性二态变化调节内分泌细胞的形成和功能。
Imprinting control region (ICR1) controls the expression of the Igf2 and H19 genes in a parent-of-origin specific manner. Appropriate expression of the Igf2-H19 locus is fundamental for normal fetal development, yet the importance of ICR1 in the placental production of hormones that promote maternal nutrient allocation to the fetus is unknown. To address this, we used a novel mouse model to selectively delete ICR1 in the endocrine junctional zone (Jz) of the mouse placenta (Jz-ΔICR1). The Jz-ΔICR1 mice exhibit increased Igf2 and decreased H19 expression specifically in the Jz. This was accompanied by an expansion of Jz endocrine cell types due to enhanced rates of proliferation and increased expression of pregnancy-specific glycoprotein 23 in the placenta of both fetal sexes. However, changes in the endocrine phenotype of the placenta were related to sexually-dimorphic alterations to the abundance of Igf2 receptors and downstream signalling pathways (Pi3k-Akt and Mapk). There was no effect of Jz-ΔICR1 on the expression of targets of the H19-embedded miR-675 or on fetal weight. Our results demonstrate that ICR1 controls placental endocrine capacity via sex-dependent changes in signalling. Summary: Imprinting at Igf2-H19 ICR1 regulates endocrine cell formation and function via sexually-dimorphic changes in Pi3k-Akt and Mapk signalling in the mouse.
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