EXPRESSION OF EPIDERMAL GROWTH-FACTOR, TRANSFORMING GROWTH-FACTOR-ALPHA, AND THEIR COMMON RECEPTOR GENES IN HUMAN UMBILICAL CORDS

Epidermal growth factor (EGF) and transforming growth factor-cu (TGF alpha), present in amniotic fluid and/or in fetal blood, could potentially regulate cord functions. The present study investigated the possible presence of functional receptors and EGF and TGF alpha themselves in umbilical cord. The reverse transcription-polymerase chain reaction followed by Southern blotting demonstrated that human umbilical cords contain EGF, TGF alpha, and EGF/TGF alpha messenger ribonucleic acid (mRNA) transcripts. In situ hybridization revealed that these mRNA transcripts are present in vascular endothelial cells and smooth muscle, amnion, and myofibroblasts in Wharton's jelly. Western immunoblotting showed that the cords contain a 170-kilodalton EGF/TGF alpha receptor protein. Immunocytochemistry demonstrated that all of the cells that contained mRNA transcripts also contained corresponding proteins. Umbilical amnion contains more EGF, TGF alpha, and their receptors than any other part of the cord. In the cord, the fetal and middle portions contain more than the placental portion or the vessels inside the placental tissue. The cord receptors can bind [I-125]EGF, stimulate receptor autophosphorylation, and increase cyclooxygenase-1 and -2 and prostaglandin E(2), suggesting that the receptors are functional. In summary, our study demonstrates that human umbilical cord expresses EGF, TGF alpha, and their common receptor genes. The cord EGF/TGF alpha receptors are functional in terms of binding of EGF, activation of receptor autophosphorylation, and increasing the formation of vasoconstrictive eicosanoid. Thus, EGF, TGF alpha, and their receptors could be one of the determinants of human fetal growth and development by autocrine, paracrine, and endocrine actions in umbilical cord.