Gene expression profiling of conditional ablation of Indian hedgehog in the mouse uterus

Conditional ablation of Indian hedgehog (Ihh) in the murine uterus results in mice that are sterile due to defects in embryo implantation. We performed microarray analysis on these mice at the time point at which the Ihh target genes are induced by the administration of exogenous hormone to mimic day 3.5 of pregnancy. This analysis identified 863 genes altered by the conditional ablation of Ihh. Of these, genes that regulated the cell cycle were overrepresented. In addition, genes involved in epidermal growth factor (EGF) and estrogen (E2) signaling were found to be deregulated upon Ihh ablation. Furthermore, upon conditional ablation of Ihh, 15 month old mice exhibited hallmarks of estrogenized uteri such as cystically dilated glands and hyalinized stroma. Thus, Ihh regulates embryo implantation by impacting the cell cycle, EGF signaling, and E2 signaling. Keywords: two group comparison We conditionally ablated Indian hedgehog in the mouse uterus using the PRcre mouse model (PRcre/+Ihhf/f; Ihhd/d). High density DNA microarray analysis was performed on Day -1 of the artificial decidual response on Ihhf/f and Ihhd/d uteri.