Angiopoietin-like gene expression in the mouse uterus during implantation and in response to steroids.

The purpose of this work was to determine if and where Angiopoietin-like genes are expressed in the mouse uterus during the implantation period of pregnancy and to determine if uterine expression of such genes is controlled by estrogen or progesterone. We found that all six known murine angiopoietin-like genes were expressed in the mouse uterus during implantation. The expression of four genes was controlled by either estrogen or progesterone. Only the levels of angiopoietin-like 4 (Angptl4) mRNA dramatically increased in implantation segments of the uterus during decidualization and was conceptus-independent. Due to this increased expression and the fact that angiopoietin-like 4 protein plays a role in lipid metabolism and angiogenesis in other tissues, only the expression of Angptl4 was further examined in the uterus and developing placenta. Angptl4 mRNA was localized to subpopulations of the endometrial stromal fibroblast and endothelial cell populations during decidualization. It was also localized to the ectoplacental cone, trophoblast giant cells and parietal endoderm of the conceptus at this time. By mid-pregnancy, Angptl4 mRNA was localized mainly to the mesometrial lymphoid aggregate region plus mesometrial endothelial cells of the uterus, as well as in various cell types of the conceptus. Additional work showed that Angptl4 expression increases in mouse endometrial stromal cells as they undergo decidualization in vitro. As in other cell types, the expression of Angptl4 in endometrial stromal cells was increased in response to an agonist of the peroxisome proliferator activated receptors. Taken together, the results of this work support the hypothesis that locally expressed Angptl4 might play a role in local uterine/placental lipid metabolism and vascular changes during implantation and thus provide a basis for future research.