Delta-Like Ligand (DLL)1 Expression in Early Mouse Decidua and Its Localization to Uterine Natural Killer Cells

Karina Y Degaki,Aureo T Yamada,Zhilin Chen,B Anne Croy,Hyunjung Lim

doi:10.1371/journal.pone.0052037

Karina Y Degaki, Aureo T Yamada + Show 3 more

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https://doi.org/10.1371/journal.pone.0052037

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Journal: PloS one	Publication Date: Dec 28, 2012
Citations: 77	License type: CC BY 4.0

Affiliation: Universidade Estadual de Campinas, Queen's University

Abstract

Uterine vascular changes, critical for pregnancy success, occur at each implant site during endometrial decidualization. Mesometrial decidualization recruits high numbers of angiogenic, uterine Natural Killer (uNK) cells that trigger midpregnancy spiral arterial remodeling. We postulated that uNK cells contribute to early decidual angiogenesis as endothelial-cell extrinsic sources of Delta-like ligand 1 (DLL1), a molecule that induces endothelial tip cell differentiation and orthogonal vascular growth in other tissues. Virgin uteri expressed Dll1 mesometrially and anti-mesometrially and relative expression increased in both anatomic regions as pregnancy progressed. Analyses of transcripts from gd10.5 uNK cells flow sorted on the basis of expression of Dolichos biflorus agglutinin (DBA) lectin revealed that DBA+ but not DBA- uNK cells expressed Dll1. Immunostaining at gd4.5 found DLL1-expressing cells rare. At gd6.5, DBA+ uNK cells at all stages of maturation expressed DLL1. By gd10.5, DLL1 immunoreactivity was strongly expressed by some but not all DBA+ uNK cells and more weakly by DBA- cells. DLL1+ cells were mesometrially stratified and concentrated within central decidua basalis. Our data suggest that uNK cells have the potential to induce endothelial tip cell differentiation and to promote non-planar vascular growth within early decidua basalis.

Highlights

The mammalian Notch signaling pathway is composed of four receptors (Notch 1–4) and five ligands (Jagged1 and 2 and Deltalike ligand (DLL) 1, 3 and 4)
That observation made in intact, viable implant sites challenged a number of widely held ideas concerning direct receptor-ligand and cell contact interactions between trophoblasts and the uterine Natural Killer (uNK) cells recruited to early decidua basalis
By gd14.5, vascular endothelial growth factor (VEGF)+Dolichos biflorus agglutinin (DBA)+ uNK cells were 30% of the DBA lectin+ uNK cells and total uNK cell numbers had dropped suggesting the angiogenic roles of uNK cells regress after mid gestation [28]

Summary

Introduction

The mammalian Notch signaling pathway is composed of four receptors (Notch 1–4) and five ligands (Jagged and 2 and Deltalike ligand (DLL) 1, 3 and 4). Notch uses cell contact-dependent signaling mechanisms triggered by the binding of Notch ligands to their receptors [1]. Notch activity in endothelial cells is essential for mouse development and successful pregnancy with the receptors Notch and Notch and the ligands Jagged, DLL1 and DLL4 having major expression [2,3]. Jagged plays roles in vascular smooth muscle development essential for postnatal survival [5,6]. Studies of neonatal retinal vessels using Dll heterozygotes identified reduced endothelial tip cell development and impaired vascular branching in deeper layers compared with +/+ controls. DLL1 was shown to be a product of extravascular cells [1]

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