Single cell RNA sequencing analysis of Mig-6 mutant mouse reveals progesterone susceptibility genes for uterine receptivity

The majority of pregnancy losses result from implantation failure. Successful embryo implantation involves a delicate interaction between the receptive uterus and an implantation-competent blastocyst. Understanding the mechanisms regulating the endometrial receptivity during preimplantation are essential for improving pregnancy outcomes. Mitogen-inducible gene 6 (MIG-6) is a key mediator of progesterone signaling in the endometrium.MIG-6 loss results in implantation failure due to non-receptive endometrium. We applied single cell RNA sequencing to determine the composition of different cell types and functions within non-receptive endometrium from uterine specific Mig-6 knock-out (Pgrcre/+Mig-6f/f; Mig-6d/d) mice. Mig-6d/d mice revealed altered gene expression in the epithelial and stromal cells. We identified key gene expression changes in the non-receptive endometrium of Mig-6d/d mice, providing valuable insights into the role of progesterone signaling in implantation. Overall design: At pregnancy day 3.5, the scRNA-seq was performed using Mig-6f/f and Mig-6d/d (Pgrcre/+ Mig-6f/f) mouse uterus (n=1). Immunohistochemistry was done to varify the changes between clusters Mig-6f/f and Mig-6d/d.