FUNCTIONAL CYTOLOGY OF THE PLACENTA AND FETAL MEMBRANES

在人类和非人类灵长类动物中，绝大多数母婴 交换是由胎盘调节的。因此，这是根本性的。 对我们理解胎儿营养和新生儿健康的重要性 关于确定胎盘选择性作用机制的问题 从母体血液中吸收物质并将它们输送到 胎儿。分离母体和胎儿血液的主要成分 它们是：1)合体滋养细胞；2)基底膜；3)胎儿毛细血管。 这项提案中包含的实验将检查各种 其中每个组件的结构和功能方面，特别是 因为它们与吸收和渗透性有关。受体介导 内吞作用是细胞的一种重要机制，包括 滋养层细胞，从它们的环境中吸收大分子。这一过程 将通过超微结构和生化相结合的方法进行详细检查 方法为了定量测定不同种类的 配体与滋养层细胞相互作用，在超微结构和 免疫细胞化学方法确定细胞内途径 配体和它们的受体。所选择的配体包括免疫球蛋白，因为 它在为胎儿提供被动免疫方面的重要性，因为低密度脂蛋白 它作为激素合成和转铁蛋白前体的重要性，因为 它在向胎儿运送铁的过程中扮演的角色。因为潜在的 细胞骨架在许多细胞功能中的重要作用，包括 内吞作用，其他研究将确定其组成和定位 免疫荧光法检测人胎盘主要细胞骨架蛋白 超微结构免疫细胞化学方法。除了……之外 大分子，离子向发育中的胎儿的运输是另一种 极其重要的胎盘功能。为了更好地理解 与胎盘活性离子转运相关的亚细胞结构 将定位人胎盘中的Na+，K+ATPase，Ca++ATPase和Ca++ 超结构细胞化学。的结构和功能基础 将研究滋养层和羊膜基底膜的通透性。孤立 基底板将暴露于具有和不具有选择性的示踪蛋白 去除基底板将暴露于示踪蛋白，无论有没有 选择性切除基底膜糖胺聚糖，尤其是肝素 以确定这些成分是否会影响渗透率。最后， 胎儿末梢毛细血管床的三维布置 人类和非人灵长类动物的中间胎盘绒毛将是 检查以确定它们的结构组织可能会如何影响 母婴交换。

In humans and non-human primates, the vast majority of maternal-fetal exchanges are mediated by the placenta. It is, therefore, of fundamental importance to our understanding of fetal nutritional and neonatal health problems to ascertain the mechanisms by which the placenta selectively absorbs substances from the maternal blood and transports them to the fetus. The major components separating the maternal and fetal bloodstreams are: 1) syncytial trophoblast 2) a basal lamina and 3) fetal capillaries. The experiments encompassed in this proposal will examine various structural and functional aspects of each of these components, especially as they relate to absorption and permeability. Receptor-mediated endocytosis is one important mechanism by which cells, including trophoblast, take up macromolecules from their environment. This process will be examined in detail by combined ultrastructural and biochemical methods in order to quantitatively detemine the manner in which various ligands interact with trophoblast, and ultrastructurally and immunocytochemically to determine the intracellular pathways followed by ligands and their receptors. The ligands selected include IgG, because of its importance in providing passive immunity to the fetus, LDL because of its importance as a precursor for hormone synthesis and transferrin because of its role in iron transport tothe fetus. Because of the potentially important role of the cytoskeleton in many cellular functions, including endocytosis, other studies will determine the composition and localization of major cytoskeletal proteins in human placenta using immunofluorescent and ultrastructural immunocytochemical methods. In addition to macromolecules, the transport of ions to the developing fetus is another vitally important placental function. In order to better understand the subcellular structures associated with active ion transport by placenta we will localize Na+, K+ ATPase, Ca++ ATPase, and Ca++ in human placenta using ultratructural cytochemistry. The structural and functional basis of trophoblast and amnion basal lamina permeability will be studied. Isolated basal laminas will be exposed to tracer proteins with and without selective removal of basal lamina will be exposed to tracer proteins with and without selective removal of basal lamina glycosaminoglycans, particularly heparan sulfate to determine if these components influence permeability. Finally, the three-dimensional arrangement of the fetal capillary bed in terminal and intermediate human and non-human primate placental villi will be examined in order to determine how their structural organization may affect maternal-fetal exchange.