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Submitted on March 5, 2007
Accepted on March 30, 2007
Center for Animal Biotechnology and Genomics (K.H., R.C.B., F.W.B., T.E.S.), Department of Animal Science (K.H., F.W.B., T.E.S.), and Image Analysis Laboratory and Department of Veterinary Integrative Biosciences (R.C.B.), Texas A&M University, College Station, Texas 77843
* To whom correspondence should be addressed. E-mail: tspencer{at}tamu.edu.
WNTs are involved in critical developmental and growth processes in animals. These studies investigated WNT pathways in the ovine uterus and conceptus during peri-implantation period of pregnancy. WNT2 and WNT2B mRNAs were detected in endometrial stroma. WNT5A and WNT5B mRNAs were most abundant in the stroma and less so in the luminal epithelium, whereas WNT11 mRNA was detected primarily in the glands. WNT7A mRNA was present in the luminal epithelium on Day 10, absent on Days 12 and 14, and increased between Days 16 and 20. Only WNT2, WNT2B, and WNT4 were detected in conceptus trophectoderm. Frizzled receptor (FZD6/8) and GSK3B mRNAs were detected primarily in endometrial epithelia and conceptus trophectoderm, whereas the LRP5/6 co-receptor was present in all endometrial cells and the trophectoderm. Dickkopf (DKK1), a WNT signaling inhibitor, increased in the endometrium from Days 16 to 20. CTNNB1 and CDH1 mRNAs were most abundant in the endometrial epithelia and trophectoderm. LEF1 mRNA was expressed primarily in uterine epithelia, whereas TCF7L2 was only in the conceptus. CTNNB1 and TCF7L2 proteins were both abundant in the nuclei of trophoblast giant binucleate cells. WNT7A stimulated a TCF/LEF-luciferase reporter activity in ovine trophectoderm cells which was inhibited by dominant negative TCF and Sfrp2. WNT7A increased trophectoderm cell proliferation as well as MSX2 and MYC mRNA levels. Wnt5a increased trophectoderm cell migration in a Rho kinase-dependent manner. These results support the hypotheses that canonical and non-canonical WNT signaling pathways are conserved regulators of conceptus-endometrial interactions in mammals and regulate peri-implantation ovine conceptus development.
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