Implantation-related expression of epidermal growth factor family molecules and their regulation by progesterone in the pregnant rat

The uterine expressions of epidermal growth factor (EGF) family are examined to elucidate their exact role(s) in rat pregnancy. EGF and its receptors' (EGF-R) mRNA levels increased significantly at implantation after which their expression gradually decreased. Heparin-binding EGF (HB-EGF) and transforming growth factor-alpha (TGF-alpha) showed a modest expression at gestation day (GD), GD4 and GD3, respectively, but were much strongly expressed at mid-pregnancy. Amphiregulin (Areg) was strongly expressed around implantation (GD4) and at mid-pregnancy (GD12). Treatment of pregnant rats with RU486 at GD5 or GD8 blocked the expression of all the genes, and administration of immature rats with progesterone (P4) induced the uterine expression of all the genes except HB-EGF. In addition, HB-EGF,TGF-alpha, and Areg proteins in the uterine and glandular epitheliums may participate in mid-pregnancy. Taken together, all of these activities are likely to be controlled by P4 in the uterus of pregnant rats.