TY - JOUR
T1 - Genome-wide gene expression profiling reveals aberrant MAPK and Wnt signaling pathways associated with early parthenogenesis
AU - Liu, Na
AU - Enkemann, Steven A
AU - Liang, Ping
AU - Hersmus, Remko
AU - Zanazzi, Claudia
AU - Huang, Junjiu
AU - Wu, Chao
AU - Chen, Zhisheng
AU - Looijenga, Leendert H J
AU - Keefe, David L
AU - Liu, Lin
PY - 2010/12
Y1 - 2010/12
N2 - 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.
AB - 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.
KW - Animals
KW - Blastocyst/metabolism
KW - Embryo, Mammalian/metabolism
KW - Female
KW - Gene Expression Profiling
KW - Gene Regulatory Networks
KW - Genome
KW - Glycogen Synthase Kinase 3/antagonists & inhibitors
KW - Indoles/pharmacology
KW - MAP Kinase Signaling System
KW - Mice
KW - Mice, Inbred C57BL
KW - Mitogen-Activated Protein Kinase 1/metabolism
KW - Mitogen-Activated Protein Kinases/metabolism
KW - Oximes/pharmacology
KW - Parthenogenesis/genetics
KW - Pregnancy
KW - RNA, Long Noncoding
KW - RNA, Untranslated/metabolism
KW - Signal Transduction
KW - Wnt Proteins/metabolism
KW - X Chromosome
UR - http://www.scopus.com/inward/record.url?scp=79951469801&partnerID=8YFLogxK
U2 - 10.1093/jmcb/mjq029
DO - 10.1093/jmcb/mjq029
M3 - Article
C2 - 20926514
SN - 1759-4685
VL - 2
SP - 333
EP - 344
JO - Journal of molecular cell biology
JF - Journal of molecular cell biology
IS - 6
ER -