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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Igf2-H19 ICR1 印记的丧失通过小鼠信号通路中性别特异性的改变增强胎盘内分泌能力
DOI：
10.1101/2021.05.14.444241
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Aykroyd B
中科院分区：
文献类型：
--
作者：
Aykroyd B
印记控制区(ICR1)以亲本来源特异性的方式控制Igf2和H19基因的表达。Igf2-H19基因的适当表达是胎儿正常发育的基础，但ICR1在胎盘分泌促进母体营养分配给胎儿的激素中的重要性尚不清楚。为了解决这一问题，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连接区(JZ-ΔICR1)中的ICR1.JZ-ΔICR1小鼠表现出特异性的JZ-Igf2表达增加和H19表达降低。随之而来的是JZ内分泌细胞类型的扩张，这是由于增殖率增加和妊娠特异性糖蛋白23在男女胎儿胎盘中的表达增加。然而，胎盘内分泌表型的变化与Igf2受体和下游信号通路(PI3K-Akt和MAPK)丰度的性别二态变化有关。JZ-ΔICR1对H19-miR-675靶基因的表达及胎儿体重无影响。我们的结果表明，ICR1通过性别相关的信号变化来控制胎盘内分泌能力。
Imprinting control region (ICR1) controls the expression of theIgf2andH19genes in a parent-of-origin specific manner. Appropriate expression of theIgf2-H19locus 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 increasedIgf2and decreasedH19expression 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 theH19-embedded miR-675 or on fetal weight. Our results demonstrate that ICR1 controls placental endocrine capacity via sex-dependent changes in signalling.
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影响因子：
3.7
作者：
Ngala RA;Fondjo LA;Gmagna P;Ghartey FN;Awe MA
通讯作者：
Awe MA
影响因子：
3.8
作者：
Sferruzzi-Perri AN;Lopez-Tello J;Napso T;Yong HEJ
通讯作者：
Yong HEJ
c-Jun N 末端激酶分子靶向治疗可阻止小鼠腹主动脉瘤形成
DOI：
--
发表时间：
2004
期刊：
脈管学 44(9)
影响因子：
--
作者：
Sumi S.;et al.;吉村耕一
通讯作者：
吉村耕一
DOI：
10.1152/ajpendo.00344.2006
发表时间：
2007-05-01
影响因子：
5.1
作者：
Ganguly, Amit;McKnight, Robert A.;Devaskar, Sherin U.
通讯作者：
Devaskar, Sherin U.
影响因子：
20.3
作者：
John I. Jones;D. Clemmons
通讯作者：
John I. Jones;D. Clemmons