Insulin-Like Growth Factor II Activates Phosphatidylinositol 3-Kinase-Protooncogenic Protein Kinase 1 and Mitogen-Activated Protein Kinase Cell Signaling Pathways, and Stimulates Migration of Ovine Trophectoderm Cells

Center for Animal Biotechnology and Genomics, Department of Animal Science, Texas A&M University, College Station, Texas 77843-2471, USA.
Endocrinology (Impact Factor: 4.64). 07/2008; 149(6):3085-94. DOI: 10.1210/en.2007-1367
Source: PubMed

ABSTRACT IGF-II, a potent stimulator of cellular proliferation, differentiation, and development, regulates uterine function and conceptus growth in several species. In situ hybridization analyses found that IGF-II mRNA was most abundant in the caruncular endometrial stroma of both cyclical and pregnant ewes. In the intercaruncular endometrium, IGF-II mRNA transitioned from stroma to luminal epithelium between d 14 and 20 of pregnancy. IGF-II mRNA was present in all cells of the conceptus but was particularly abundant in the yolk sac. Immunohistochemical analyses revealed that phosphorylated (p)-protooncogenic protein kinase 1, p-ribosomal protein S6 kinase, p-ERK1/2, and p-P38 MAPK proteins were present at low levels in a majority of endometrial cells but were most abundant in the nuclei of endometrial luminal epithelium and conceptus trophectoderm of pregnant ewes. In mononuclear trophectoderm cells isolated from d-15 conceptuses, IGF-II increased the abundance of p-pyruvate dehydrogenase kinase 1, p-protooncogenic protein kinase 1, p-glycogen synthase kinase 3B, p-FK506 binding protein 12-rapamycin associated protein 1, and p-ribosomal protein S6 kinase protein within 15 min, and the increase was maintained for 90 min. IGF-II also elicited a rapid increase in p-ERK1/2 and p-P38 MAPK proteins that was maximal at 15 or 30 min posttreatment. Moreover, IGF-II increased migration of trophectoderm cells. Collectively, these results support the hypothesis that IGF-II coordinately activates multiple cell signaling pathways critical to survival, growth, and differentiation of the ovine conceptus during early pregnancy.

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    • "The maternally imprinted insulin-like growth factor II (IGF-II) gene on bovine chromosome 29 is one of the best characterized epigenetically regulated loci (Goodall & Schmutz, 2003; Gebert et al., 2009). Insulinlike growth factors have been shown to play important roles in early embryonic (Rappolee et al., 1992; Wang et al., 2009), placental, and fetal development (Sibley et al., 2004; Su et al., 2011), probably through combined activation of multiple cell signaling pathways critical to survival, growth, and differentiation (Kim et al., 2008). In addition, the IGF-II gene provides an excellent model for studying RNA involvement in maintenance of nucleosome-retained regions of the sperm chromatin in spite of nearly complete replacement of DNA-bound histones with protamines (Jenkins & Carrell, 2011). "
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