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Studies to date have demonstrated epidermal growth factor (EGF) receptors primarily on the outer plasma membrane of the human placental syncytiotrophoblasts facing maternal blood and to a lesser extent on the cytotrophoblast stem cells. In the present studies, first- and third-trimester human placental tissues were immunostained with monoclonal antibodies (MAb) to the EGF binding domain of the human EGF receptor or to the activated (tyrosine-phosphorylated) human EGF receptor. Cytotrophoblasts, syncytiotrophoblasts, and fetal connective tissue cells in first-trimester tissues immunostained with both MAb, with the notable exception of the absence of staining of activated EGF receptor over cytotrophoblast plasma membranes. In contrast, staining of third-trimester placentas with either MAb yielded little to no staining of either trophoblast cell layer but intense staining of fetal connective tissue cells. Staining for EGF receptors over cytotrophoblasts in the first trimester is consistent with the hypothesis that maternal EGF or TGF-alpha derived from the endometrium or placenta may be the mitogen responsible for cytotrophoblast cell division and that the receptors localized to the syncytiotrophoblast are involved in EGF regulation of differentiated function. The absence of heavy staining of activated EGF receptor on trophoblast plasma membranes in third-trimester placentas is consistent with down-regulation of EGF receptor activity.

Localization of epidermal growth factor receptors in first- and third-trimester human placentas.