Increased binding of epidermal growth factor at preimplantation sites in mouse uteri

The presence of receptors for epidermal growth factor (EGF) in nonpregnant uteri and the elevation of EGF levels in blood during early pregnancy suggest that EGF and its receptor may play important roles in the early stages of pregnancy. We determined the distribution of EGF receptors in uteri of nonpregnant and pregnant mice during the late preimplantation period (days 4.5-5.0 of pregnancy) using radioautograph and quantitative binding techniques. Radioautography of [125I]EGF binding to cornua from nonpregnant mice showed low levels of specific binding evenly distributed throughout the cornua. In contrast, radioautographs of cornua from pregnant mice showed bands of elevated binding encircling the lumen at sites of preimplantation. Results from radioautography were supported by quantitative analysis of [125I]EGF binding to uterine homogenates from nonpregnant and pregnant mice. Binding of [125I]EGF to uterine membranes was highly specific and time dependent. The average level of specific EGF binding calculated from Scatchard plots of nonpregnant uteri (27 +/- 13 fmol/mg protein) was significantly (P less than 0.05) lower than that in pregnant superovulated uteri (106 +/- 67 fmol/mg protein). Furthermore, specific binding of EGF was significantly (P less than 0.05) higher in preimplantation sites than in the intervening nonimplantation regions from the same uteri (42 +/- 6 vs. 29 +/- 4 fmol/mg protein, respectively). Differences in EGF binding appear to be due to changes in the number of EGF receptors, since half-displacement values (1 nM) were similar in all samples. These results demonstrate that alterations of EGF receptor levels occur at sites where implantation will occur in mouse uteri and support the concept that the transforming growth factor-alpha/EGF receptor and its ligands are involved in implantation of concepti.