Loss of GRB2 results in nonreceptive endometrium and female infertility.

To understand the role of GRB2 in the uterus, we generated mice with conditional ablation of Grb2 in the PGR positive cells (Pgrcre/+Grb2f/f; Grb2d/d). Grb2d/d mice are infertile due to implantation failure. Although ovarian functions are normal, Grb2d/d mice had non-receptive endometrium due to dysregulation of progesterone and estrogen signaling. Our transcriptomic analysis identified deficiency of progesterone and FOXA2 signaling. We used RNA-sequencing to determine the differences in uterine gene expression resulting from deletion of endometrial Grb2.