Primary decidual zone formation requires Scribble for pregnancy success in mice

Jia Yuan,Xiaofei Sun,Gerd Walz,Wenbo Deng,Amanda Bartos,Tobias B Huber,Sudhansu K Dey,Florian Grahammer,Shizu Aikawa

doi:10.1038/s41467-019-13489-4

Abstract

Scribble (Scrib) is a scaffold protein with multifunctional roles in PCP, tight junction and Hippo signaling. This study shows that Scrib is expressed in stromal cells around the implantation chamber following implantation. Stromal cells transform into epithelial-like cells to form the avascular primary decidual zone (PDZ) around the implantation chamber (crypt). The PDZ creates a permeability barrier around the crypt restricting immune cells and harmful agents from maternal circulation to protect embryonic health. The mechanism underlying PDZ formation is not yet known. We found that uterine deletion of Scrib by a Pgr-Cre driver leads to defective PDZ formation and implantation chamber (crypt) formation, compromising pregnancy success. Interestingly, epithelial-specific Scrib deletion by a lactoferrin-Cre (Ltf-Cre) driver does not adversely affect PDZ formation and pregnancy success. These findings provide evidence for a previously unknown function of stromal Scrib in PDZ formation, potentially involving ZO-1 and Hippo signaling.

Highlights

Scribble (Scrib) is a scaffold protein with multifunctional roles in PCP, tight junction and Hippo signaling
Our previous study shows that Scrib has a distinct expression pattern at the apical surface of uterine epithelial cells in early stages of pregnancy followed by increasing expression in stromal cells around the blastocyst at the implantation site[4]
We consistently found that Scribf/fPgrcre/+ mice show smaller implantation sites on day 6 due to the failure of primary decidual zone (PDZ) formation (Fig. 6a)

Summary

Introduction

Scribble (Scrib) is a scaffold protein with multifunctional roles in PCP, tight junction and Hippo signaling. This process is initiated at the antimesometrial (AM) pole with the transformation of stromal cells into epithelial-like cells (epithelioid cells) surrounding the epithelium of the crypt (implantation chamber) that houses the blastocyst This zone is called the primary decidual zone (PDZ), first identified by Krehbiel[5] as an avascular zone and thought to function as a transient, size-dependent permeable barrier to protect the embryo from harmful agents, such as immunoglobulins, immune cells, microorganisms, and other noxious agents[6]. This zone begins to form from day 5 afternoon and becomes fully established on day 6 with the loss of the crypt epithelium[7]. Scrib ceases to express in the luminal epithelium with distinct expression in the stroma surrounding the implantation chamber[4]

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Conclusion