LOCALIZATION OF TRANSFORMING GROWTH-FACTOR-BETA AT THE HUMAN FETAL-MATERNAL INTERFACE - ROLE IN TROPHOBLAST GROWTH AND DIFFERENTIATION
LOCALIZATION OF TRANSFORMING GROWTH-FACTOR-BETA AT THE HUMAN FETAL-MATERNAL INTERFACE - ROLE IN TROPHOBLAST GROWTH AND DIFFERENTIATION
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DOI：
10.1095/biolreprod46.4.561
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发表时间：
1992-04-01
影响因子：
3.6
通讯作者：
LALA, PK
中科院分区：
文献类型：
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作者：
GRAHAM, CH;LYSIAK, JJ;LALA, PK
我们检查了转化生长因子 (TGF)-β 在妊娠早期和足月人类蜕膜和绒毛膜绒毛中的定位，并探讨了该因子对培养的滋养层细胞增殖和分化的作用。 两种抗体，1D11.16.8（一种能够识别 TGF-β-1 和 TGF-β-2 的小鼠单克隆中和抗体）和 CL-B1/29（一种能够识别 TGF-β-2 的兔多克隆抗体），用于在固定、石蜡包埋或固定、冷冻的胎盘和蜕膜切片中免疫定位 TGF-β，提供了相似的结果。 在妊娠早期蜕膜的细胞外基质（ECM）和足月蜕膜细胞的细胞质中观察到强烈的标记。 妊娠早期和足月胎盘的合体滋养层细胞的细胞质以及绒毛膜绒毛核心的 ECM 均显示出中等程度的标记。 在足月胎盘的细胞滋养层外壳中观察到强细胞质标记。 为了检查 TGF-β 对滋养层增殖和分化的作用，建立了妊娠早期滋养层细胞的早期传代培养物和足月滋养层细胞的原代培养物，并基于大量免疫细胞化学和功能标记物进行了表征。 这些细胞表达细胞角蛋白、胎盘碱性磷酸酶、尿激酶型纤溶酶原激活剂和妊娠特异性β糖蛋白，但不表达因子VIII或63D3；他们还生产 hCG 和 IV 型胶原酶。 将妊娠早期滋养层培养物暴露于 TGF-β-1 会以剂量依赖性方式显着抑制增殖。 TGF-β-2 存在时也具有抗增殖作用。 在存在中和性抗 TGF-β 抗体 (1D11.16.8) 的情况下，这些效应以浓度依赖性方式被消除。 在为期 3 天的培养中，外源 TGF-β-1 刺激妊娠早期多核细胞以及足月滋养层细胞的形成。 向妊娠早期滋养层细胞添加中和性抗 TGF-β 抗体，在 24 小时培养中刺激增殖超出对照水平，并在 3 天培养中减少多核细胞的形成，表明内源性 TGF-β 活性的存在。 这些结果表明，人胎儿-母体界面处产生的TGF-β在滋养层的增殖和分化中起主要调节作用。
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.