To prepare for embryo implantation, the uterus must undergo a series of reciprocal interactions between the uterine epithelium and the underlying stroma, which are orchestrated by ovarian hormones. During this process, multiple signaling pathways are activated to direct cell proliferation and differentiation, which render the uterus receptive to the implanting blastocysts. One important modulator of these signaling pathways is the cell surface and extracellular matrix macromolecules, heparan sulfate proteoglycans (HSPGs). HSPGs play crucial roles in signal transduction by regulating morphogen transport and ligand binding. In this study, we examine the role of HSPG sulfation in regulating uterine receptivity by conditionally deleting the N-deacetylase/N-sulfotransferase (NDST) 1 gene (Ndst1) in the mouse uterus using the Pgr-Cre driver, on an Ndst2- and Ndst3-null genetic background. Although development of the female reproductive tract and subsequent ovarian function appear normal in Ndst triple-knockout females, they are infertile due to implantation defects. Embryo attachment appears to occur but the uterine epithelium at the site of implantation persists rather than disintegrates in the mutant. Uterine epithelial cells continued to proliferate past day 4 of pregnancy, accompanied by elevated Fgf2 and Fgf9 expression, whereas uterine stroma failed to undergo decidualization, as evidenced by lack of Bmp2 induction. Despite normal Indian hedgehog expression, transcripts of Ptch1 and Gli1, both components as well as targets of the hedgehog (Hh) pathway, were detected only in the subepithelial stroma, indicating altered Hh signaling in the mutant uterus. Taken together, these data implicate an essential role for HSPGs in modulating signal transduction during mouse implantation.
Pubmed ID: 29688404 RIS Download
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This unknown targets phospho-Histone H3 (Ser10)
View all literature mentionsThis monoclonal targets Ab-10E4 ab1-hs anti-HS H1890 anti-heparan sufate anti-heparan sulfate
View all literature mentionsThis polyclonal secondary targets IgG
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
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View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis monoclonal targets Heparan sulfate
View all literature mentionsThis polyclonal targets IgG
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG
View all literature mentionsThis monoclonal targets Ab-10E4 ab1-hs anti-HS H1890 anti-heparan sufate anti-heparan sulfate
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis recombinant monoclonal targets GAPDH
View all literature mentionsThis unknown targets phospho-Histone H3 (Ser10)
View all literature mentionsThis monoclonal targets E-cadherin
View all literature mentions