Localization of transforming growth factor β and its natural inhibitor decorin in the human placenta and decidua throughout gestation

Transforming growth factor β (TGFβ) produced at the human fetomaternal interface has been shown to play a crucial role in controlling trophoblast invasion of the uterus. Decorin, a naturally occurring chondroitin-dermatan sulphate proteoglycan which binds TGFβ can inhibit its activity. In this study, immunohistochemical techniques were used to determine the locations of TGFβ and decorin within the human placenta and decidua throughout normal gestation. In addition, sites of TGFβ 1 mRNA synthesis were identified in early and late placenta by in situ hybridization. Results revealed the presence of immunoreactive TGFβ in the cytoplasm of villous syncytiotrophoblast and extravillous trophoblast cells throughout gestation. TGFβ immunostaining was absent from villous cytotrophoblast at all gestational ages examined. The extracellular matrix (ECM) of the villous core at all stages of gestation and cells of the cytotrophoblastic shell of the term placenta were immunoreactive for TGFβ. Within decidual tissue, TGFβ was primarily localized in the ECM during the first trimester and only a small proportion of decidual cells exhibited intracellular labelling. At later gestational ages the majority of decidual cells showed intracellular labelling accompanied by a decrease in ECM staining. This switch may reflect increased TGFβ synthesis by the decidual cells, decreased release, or altered TGFβ binding to one or more ECM proteins. In situ hybridization indicated that TGFβ 1 mRNA was primarily localized to the syncytiotrophoblast cell layer with low intensity signals present in extravillous trophoblast cells, in trophoblast cell columns, and in large decidual cells. At term, TGFβ 1 mRNA was located in both the syncytiotrophoblast and villous mesenchymal cells. Decorin was immunolocalized to the ECM of the mesenchymal core of the chorionic villi throughout gestation and no immunoreactivity was observed in either villous or extravillous trophoblast. In the first trimester decidua, decorin was localized to the ECM whereas decidual cells, decidual leucocytes, and the uterine epithelium were negative. At later gestational ages, the ECM as well as a few decidual cells displayed weak immunoreactivity. A strong co-localization of TGFβ and decorin in the ECM of first trimester decidual tissue suggests that decorin may aid TGFβ storage or limit its activity in the ECM.