Transforming growth factor-alpha in human implantation trophoblast: immunohistochemical evidence for autocrine/paracrine function.

Epidermal growth factor (EGF) and its receptor (EGF-R) have been demonstrated in human implantation sites. Transforming growth factor-alpha (TGF-alpha), a protein with extensive sequence homology to EGF and with equal affinity for the EGF-R, was localized immunohistochemically in early intrauterine and ectopic pregnancies. Within the same experiments, TGF-alpha immunostaining was more intense in ectopic than intrauterine pregnancies. In both groups, TGF-alpha immunostaining was moderate to intense in the syncytiotrophoblast (ST), light to moderate in the cytotrophoblast (CT), and moderate to intense in intermediate trophoblast (IT). In ST, TGF-alpha immunostaining localized to the cytoplasm and plasma membranes, including microvilli. No nuclear associated TGF-alpha was noted in ST. In CT, differential TGF-alpha immunostaining was noted between the villous and nonvillous CT. Villous CT demonstrated light to absent cytoplasmic TGF-alpha immunostaining with intense nuclear staining. In contrast, nonvillous CT revealed moderate to intense cytoplasmic staining without demonstrable nuclear staining. These results demonstrate the presence of immunoreactive TGF-alpha in all forms of trophoblast. The known presence of the EGF-R suggests an autocrine/paracrine role for TGF-alpha during human implantation.