title: Localization of transforming growth factor-beta at the human fetal-maternal interface: role in trophoblast growth and differentiation.
abstract: We examined the localization of transforming growth factor (TGF)-beta in first-trimester and term human decidua and chorionic villi and explored the role of this factor on the proliferation and differentiation of cultured trophoblast cells. Two antibodies, 1D11.16.8, a mouse monoclonal neutralizing antibody capable of recognizing both TGF-beta 1 and TGF-beta 2 and CL-B1/29, a rabbit polyclonal antibody capable of recognizing TGF-beta 2, were used to immunolocalize TGF-beta in fixed, paraffin-embedded, or fixed, frozen sections of placenta and decidua, providing similar results. Intense labeling was observed in the extracellular matrix (ECM) of the first-trimester decidua and cytoplasm of term decidual cells. Syncytiotrophoblast cell cytoplasm as well as the ECM in the core of the chorionic villi of both first-trimester and term placentas exhibited a moderate degree of labeling. Strong cytoplasmic labeling was observed in the cytotrophoblastic shell of the term placenta. To examine the role of TGF-beta on trophoblast proliferation and differentiation, early passage cultures of first-trimester and primary cultures of term trophoblast cells were established and characterized on the basis of numerous immunocytochemical and functional markers. These cells expressed cytokeratin, placental alkaline phosphatase, urokinase-type plasminogen activator, and pregnancy-specific beta glycoprotein, but not factor VIII or 63D3; they also produced hCG and collagenase type IV. Exposure of first-trimester trophoblast cultures to TGF-beta 1 significantly inhibited proliferation in a dose-dependent manner. An antiproliferative effect was also noted in the presence of TGF-beta 2. These effects were abrogated in the presence of the neutralizing anti-TGF-beta antibody (1D11.16.8) in a concentration-dependent manner. In a 3-day culture, exogenous TGF-beta 1 stimulated formation of multinucleated cells by the first trimester as well as term trophoblast cells. Addition of neutralizing anti-TGF-beta antibody to first-trimester trophoblast cells stimulated proliferation beyond control levels in a 24-h culture and reduced formation of multinucleated cells in a 3-day culture, indicating the presence of endogenous TGF-beta activity. These results indicate that TGF-beta produced at the human fetal-maternal interface plays a major regulatory role in the proliferation and differentiation of the trophoblast.
authors.affiliation: Department of Anatomy, University of Western Ontario, London, Canada.
authors.forename: C H
authors.initials: CH
authors.lastname: Graham
authors.forename: J J
authors.initials: JJ
authors.lastname: Lysiak
authors.forename: K R
authors.initials: KR
authors.lastname: McCrae
authors.forename: P K
authors.initials: PK
authors.lastname: Lala
mesh_terms: D000469:Alkaline Phosphatase / Q000032:analysis / Q000378:metabolism; D000911:Antibodies, Monoclonal; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002824:Chorionic Villi / Q000737:chemistry / Q000378:metabolism; D003656:Decidua / Q000737:chemistry / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005314:Embryonic and Fetal Development / Q000187:drug effects* / Q000502:physiology; D005260:Female; D005333:Fetus / Q000737:chemistry*; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000032:analysis / Q000378:metabolism; D007743:Labor, Obstetric / Q000378:metabolism; D010920:Placenta / Q000737:chemistry*; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000032:analysis* / Q000378:metabolism / Q000502:physiology*; D014327:Trophoblasts / Q000166:cytology*; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D016212:Transforming Growth Factor beta; D007633:Keratins; D000469:Alkaline Phosphatase; D014568:Urokinase-Type Plasminogen Activator