Immunohistochemical localization of transforming growth factor-beta in human implantation sites

Transforming growth factor-beta (TGF beta), a protein known to antagonize many of the functions of the epidermal growth factor-receptor system, was localized immunohistochemically in unruptured ectopic pregnancies (EP) removed by salpingectomy (n = 8), uterine decidua from EP (n = 4), and decidua and trophoblast from electively terminated first trimester pregnancies (ETP; n = 8). Two rabbit polyclonal antisera that recognize both TGF beta 1 and beta 2 were used. Immunostaining for TGF beta was identified in all three forms of trophoblast, cytotrophoblasts, intermediate trophoblasts, and syncytiotrophoblasts, which were differentiated histologically and immunohistochemically. Moderate cytoplasmic immunostaining was found in villous cytotrophoblasts in both EP and ETP. Nonvillous (anchoring) cytotrophoblasts in these same tissues demonstrated moderate immunostaining adjacent to the villous and light immunostaining distal to the villous. In intermediate trophoblasts, moderate to intense immunostaining was seen in EP and ETP. Syncytiotrophoblasts demonstrated moderate cytoplasmic immunostaining in EP and ETP as well as moderate to intense staining of plasma membranes and microvilli. Nuclear staining was not evident in any form of trophoblast. TGF beta immunostaining was demonstrated in both glands and stroma of decidua from both EP and ETP; however, staining was more intense in decidua from ETP. With the known presence of TGF beta receptors and mRNA in placenta, these results suggest an autocrine/paracrine role for TGF beta regulation of endometrial-trophoblast function during human implantation.