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This version published online on March 13, 2008
Endocrinology, doi:10.1210/en.2007-1367
A more recent version of this article appeared on June 1, 2008
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Submitted on October 18, 2007
Accepted on March 3, 2008

Insulin-like Growth Factor 2 (IGF2) Activates PI3K-AKT1 and MAPK Cell Signaling Pathways and Stimulates Migration of Ovine Trophectoderm Cells

Jinyoung Kim, Gwonhwa Song, Haijun Gao, Jennifer L. Farmer, M. Carey Satterfield, Robert C. Burghardt, Guoyao Wu, Greg A. Johnson, Thomas E. Spencer, and Fuller W. Bazer*

Center for Animal Biotechnology and Genomics, Department of Animal Science and Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, Texas 77843, USA

* To whom correspondence should be addressed. E-mail: fbazer{at}cvm.tamu.edu.

Insulin-like growth factor 2 (IGF2), a potent stimulator of cellular proliferation, differentiation and development, regulates uterine function and conceptus growth in several species. In situ hybridization analyses found that IGF2 mRNA was most abundant in the caruncular endometrial stroma of both cyclic and pregnant ewes. In the intercaruncular endometrium, IGF2 mRNA transitioned from stroma to luminal epithelium (LE) between Days 14 and 20 of pregnancy. IGF2 mRNA was present in all cells of the conceptus, but was particularly abundant in yolk sac. Immunohistochemical analyses revealed that phosphorylated AKT1 (p-AKT1), p-RPS6K, p-ERK1/2, and p-P38 MAPK proteins were present at low levels in a majority of endometrial cells, but were most abundant in nuclei of endometrial LE and conceptus trophectoderm of pregnant ewes. In mononuclear trophectoderm cells isolated from Day 15 conceptuses, IGF2 increased abundance of p-PDK1, p-AKT1, p-GSK3B, p-FRAP1, and p-RPS6K protein within 15 min and the increase was maintained for 90 min. IGF2 also elicited a rapid increase in p-ERK1/2 and p-P38 MAPK proteins that was maximal at 15 or 30 min post-treatment. Moreover, IGF2 increased migration of trophectoderm cells. Collectively, these results support the hypothesis that IGF2 coordinately activates multiple cell signaling pathways critical to survival, growth, and differentiation of the ovine conceptus during early pregnancy.


Key words: sheep • conceptus trophectoderm • insulin-like growth factor • implantation







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