Blood Trophoblast

Twenty years ago, a high-affinity-binding site for uPA was demonstrated on the surface of peripheral blood monocytes and cultured cells of the human histiocytic lymphoma cell line, U937 [46]. The expression of uPAR on the cell surface of many cell types has since then been demonstrated, including a variety of neoplastic cell lines as well as nonneoplastic cells such as neutrophils, macrophages, keratinocytes, placental trophoblasts, endothelial, and smooth muscle cells [7, 33, 47-51]. The human uPAR gene has been mapped to chromosome 19ql.3 [52]. 

The placenta develops from a portion of the zygote and thus has the same genetic endowment as the developing fetus (78). The embryonic/fetal component consists of trophoblastic-derived chorionic villi/ which invade the maternal endometrium and are exposed directly to maternal blood in lake-like structures called lacunae. These villi create the large surface area necessary for maternal-fetal transfer in what becomes the intervillous space of the placenta. Here the maternal blood pressure supplies pulsatile blood flow in jetlike streams from the spiral arteries of the endometriunX/ to bathe the chorionic villi and allow for transfer of gaseS/ nutrientS/ and metabolic products. Biologically/ the human placenta is classified as a hemochorial placenta because maternal blood is in direct contact with the fetal chorionic membrane. It is this membrane that determines what is transferred to the fetus. 

In humanS/ P-gp is expressed on trophoblastic cells throughout pregnancy (82/ 84-86). It has been located on apical surfaces of endodermal cells of the mouse yolk sac (87)/ in the vesicles of the brush border membrane of the human syncytiotrophoblast that directly faces maternal blood/ but not within maternal vascular endothelium (83/ 84/ 86-95). Actively transporting molecules in a basolateral-to-apical direction/ the role of P-gp within the placenta is similar to its function at other sites it extrudes drugs from the placenta back into maternal circulation/ thereby protecting the developing fetus from potential toxic factors within the maternal circulation (95). 

Also, hCG is useful in identifying patients with trophoblastic tumors and, together with AFP, in detecting non-seminomatous testicular tumors. Levels of hCG correlate with the tumor volume and disease prognosis. The presence of hCG in seminoma may indicate the presence of choriocarcinoma. Because hCG does not cross the blood-brain barrier, the normal cerebrospinal fluid-to-serum ratio is 1 60. Higher levels in cerebrospinal fluid may indicate metastases to the brain. Furthermore, the response to therapy for patients with central nervous system metastasis may be indicated by monitoring the hCG level. 

The placenta keeps the maternal and fetal circulation systems separate, nourishes the fetus, eliminates fetal wastes, and produces hormones vital to pregnancy. It is composed of large collections of fetal vessels called villi, which are surrounded by intervillous spaces in which maternal blood flows. For substances to move from maternal circulation to fetal circulation, they must cross through the trophoblasts and several membranes. The transfer of any substance depends largely on the concentration gradient between the maternal and fetal circulatory systems, the presence or absence of circulating binding proteins, the hpid solubility of the substance, and the presence of facilitated transport, such as ion pumps or receptor-mediated endocytosis (Box 54-1). The placenta is an effective barrier to the movement... 

Fig. 4 (A) In vitro modeling of colon cancer (B) production of cord blood cells (C) astrocyte culture for cell-based therapy of Parkinson s disease and (D) placenta model using trophoblast cells for transport.

MRPl + Syncytiotrophoblasr cells, trophoblasts. abluminal side of blood vessefs in villi Organic anion, glutathione, and glucuronide conjugate transporter transfer of unconJugated bilirubin to maternal circulation... 

The chorion is a bilaminar membrane comprised of an outer reticular layer which is similar to the amnion s stromal layer and an inner, trophoblast layer. Even though the chorion layer demonstrates a greater thickness than the amnion, it demonstrates less tensile strength than the amnion layer. The chorion contains vilh that function as the barrier between maternal and fetal blood vessels. ... 

Next, open Reichert s membrane although this is thin and transparent, it is mostly overlain with a layer of trophoblast and blood cells, and it may be necessary to pick through this layer before rupturing Reichert s membrane, after which removal is straightforward, trimming it up to, but not beyond, the placental border (Fig. 8). 

Goldbard, S. B. Sklar, L. A. Marrone, B. L. Identification and isolation of trophoblasts from maternal blood for testing for prenatal abnormalities. PCX Int. Appl. WO 9419487, 1994 Chem. Abstr. 1994, 121, 250656. 

Placental metallothionein binds zinc and copper as well as cadmium. Zinc and copper are essential nutrients for the fetus whereas cadmium is toxic to the fetus and retained rather than transferred to the fetus. There is a question, therefore, as to how the essential metals are preferentially transported to the fetus while the toxic metal, cadmium, is retained. One possibility is that there is a greater sensitivity for zinc and copper metallothionein than cadmium metallothionein to the action of proteolytic enzymes present in trophoblasts. Degradation of the zinc and copper metallothionein complex facilitates the release of these metals to fetal blood, whereas cadmium metallothionein is resistant to this effect. 

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