Primary decidual zone formation requires Scribble for pregnancy success in mice

• Published in: Nature communications 2019-11, Vol.10 (1), p.5425-10, Article 5425
• Main Authors: Yuan, Jia, Aikawa, Shizu, Deng, Wenbo, Bartos, Amanda, Walz, Gerd, Grahammer, Florian, Huber, Tobias B., Sun, Xiaofei, Dey, Sudhansu K.
• Format: Article
• Language: English
• Subjects: 14/32; 14/34; 14/63; 14/69; 38/1; 38/77; 38/88; 45/41; 631/136/3194; 631/80; 64/60; 96/95; Animals; Clonal deletion; Decidua; Decidua - cytology; Decidua - metabolism; Embryo Implantation - genetics; Embryos; Epithelial Cells - cytology; Epithelial Cells - metabolism; Female; Gene Deletion; Humanities and Social Sciences; Immune system; Implantation; Intracellular Signaling Peptides and Proteins - genetics; Lactoferrin; Mice; multidisciplinary; Permeability; Pregnancy; Protein-Serine-Threonine Kinases - metabolism; Science; Science (multidisciplinary); Signal Transduction; Signaling; Stromal cells; Stromal Cells - cytology; Stromal Cells - metabolism; Success; Uterus; Uterus - cytology; Uterus - metabolism; Zonula occludens-1 protein; Zonula Occludens-1 Protein - metabolism
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-13489-4

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. The scaffold protein Scribble (Scrib) has roles in PCP and tight junction formation. Here the authors show that during embryo implantation in mouse, Scrib is needed to form the avascular primary decidual zone by transforming stromal cells into an epithelial cell-like barrier around the crypt, protecting the embryo from harmful infiltrations.