Genome-wide Gene Expression Profiling Reveals Aberrant MAPK and Wnt Signaling Pathways Associated with Early Parthenogenesis
Genome-wide Gene Expression Profiling Reveals Aberrant MAPK and Wnt Signaling Pathways Associated with Early Parthenogenesis
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DOI：
10.1093/jmcb/mjq029
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发表时间：
2010-12-01
影响因子：
5.5
通讯作者：
Liu, Lin
中科院分区：
文献类型：
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作者：
Liu, Na;Enkemann, Steven A.;Liu, Lin
哺乳动物的孤雌生殖无法存活，但在妊娠中期流产，可能是因为缺乏父亲的基因表达。为了了解发育早期孤雌生殖失败的分子机制，我们对孤雌生殖囊胚和正常受精胚胎的囊胚进行了整体基因表达谱和功能分析。孤雌激活的囊胚有749个基因的表达发生了变化，其中214个基因的表达低于受精胚胎，而以最小的1.8倍变化为界值时，表达水平高于受精胚胎。对胎盘发育至关重要的基因在孤雌胎囊胚中的表达减少。部分母系基因表达上调，父系相关基因表达下调。此外，Wnt信号的异常增加和丝裂原激活的蛋白激酶(MAPK)信号的减少与早期孤雌生殖有关。与受精囊胚受精后120h相比，孤雌激活的囊胚中细胞外信号调节蛋白2(ERK2)的蛋白水平较低。糖原合成酶-3(GSK-3)的特异性抑制剂6-溴吲哚红-3‘-肟显著抑制胚胎孵化。几个印记基因在单性生殖囊胚中的表达发生了变化。基因表达也将Xist的表达降低与X染色体的激活联系起来。我们的研究结果表明，X失活失败、印迹异常、ERK/MAPK信号降低、Wnt信号可能升高以及胎盘发育相关基因的表达减少可能共同导致孤雌胚胎中胎盘形成异常和胎儿发育失败。
Mammalian parthenogenesis could not survive but aborted during mid-gestation, presumably because of lack of paternal gene expression. To understand the molecular mechanisms underlying the failure of parthenogenesis at early stages of development, we performed global gene expression profiling and functional analysis of parthenogenetic blastocysts in comparison with those of blastocysts from normally fertilized embryos. Parthenogenetic blastocysts exhibited changes in the expression of 749 genes, of which 214 had lower expression and 535 showed higher expressions than fertilized embryos using a minimal 1.8-fold change as a cutoff. Genes important for placenta development were decreased in their expression in parthenote blastocysts. Some maternally expressed genes were up-regulated and paternal-related genes were down-regulated. Moreover, aberrantly increased Wnt signaling and reduced mitogen-activated protein kinase (MAPK) signaling were associated with early parthenogenesis. The protein level of extracellular signal-regulated kinase 2 (ERK2) was low in parthenogenetic blastocysts compared with that of fertilized blastocysts 120 h after fertilization. 6-Bromoindirubin-3'-oxime, a specific glycogen synthase kinase-3 (GSK-3) inhibitor, significantly decreased embryo hatching. The expression of several imprinted genes was altered in parthenote blastocysts. Gene expression also linked reduced expression of Xist to activation of X chromosome. Our findings suggest that failed X inactivation, aberrant imprinting, decreased ERK/MAPK signaling and possibly elevated Wnt signaling, and reduced expression of genes for placental development collectively may contribute to abnormal placenta formation and failed fetal development in parthenogenetic embryos.