Syncytiotrophoblasts

Endothelial NO Synthase (eNOS) expression is relatively specific for endothelial cells. However, the isozyme has also been detected in certain neurons of the brain, in syncytiotrophoblasts of human placenta and in LLC-PKi kidney tubular epithelial cells. 

Although a uniform nomenclature for Na /H exchanger isoforms has not yet been adopted, we will refer to the amiloride-sensitive type of Na" /H exchanger that is present in the basolateral membrane of epithelia (apical membrane of placental syncytiotrophoblast) and also widely distributed in non-epithelial cells as the sensitive-type. The relatively amiloride-resistant isoform present in apical mem-... 

Figure 16.1 Illustration of the anatomical arrangement of the syncytiotrophoblast (placental barrier) and the fetal capillaries as would appear in a cross section of a human placental villus. Reprinted from Audus [10] with permission from Elsevier B.V.

Passive diffusion is considered to be the major pathway by which xenobiotics cross the placenta. Paracellular diffusion was shown to be the predominant pathway for transfer of hydrophilic solutes, such as chloride ions across perfused placental lobes and opioid peptides and dextrans across BeWo cells [11-13], It has been proposed that denudations in the syncytiotrophoblasts-containing fibrinoid deposits provide a possible paracellular route across the placenta [14], Transtrophoblast channels in the syncytiotrophoblasts could also be responsible for this mode of diffusion [15], For more lipophilic solutes, the transplacental route appears to be the preferred mode of passage... 

It should be mentioned that the placental villous fragments can be used to measure uptake into the syncytiotrophoblast layer but they cannot be used for trans-cellular transport studies. If the transporter is expressed in the microvillous border membrane, the effects of various factors on transporter function can be determined. Another disadvantage is that the villous fragments may be heterogenous in composition and hence, uptake experiments may not be reflective of syncytiotrophoblast uptake alone. 

Since transport across the syncytiotrophoblast layer is the rate-limiting step in the absorption of substances from the maternal circulation to the fetal, these cells can provide information on uptake processes which are subject to intracellular regulatory mechanisms or affected by intracellular metabolism. However, it is very difficult to isolate this layer because of its syncytial nature. As a result, the undifferentiated precursor cytotrophoblast cells have been isolated and cultured. These cells do not proliferate in culture, but aggregate and spontaneously differentiate into syncytiotrophoblasts [49],... 

The choriocarcinoma cell line JAr bears close resemblance to early trophoblast, as their secretion pattern of hCG and steroids is similar, and the cells can differentiate into syncytiotrophoblasts in vitro [71], In a study comparing efflux transporter expression and activity in trophoblast cell lines and choriocarcinoma cells, the expression profiles indicated that while BeWo are more... 

A. Ericsson, B. Hamark, T.L. Powell, and T. Jansson. Glucose transporter isoform 4 is expressed in the syncytiotrophoblast of first trimester human placenta. Hum Reprod. 20 521-530 (2005). 

M. Inuyama, F. Ushigome, A. Emoto, N. Koyabu, S. Satoh, K. Tsukimori, H. Nakano, H. Ohtani, and Y. Sawada. Characteristics of L-lactic acid transport in basal membrane vesicles of human placental syncytiotrophoblast. Am J Physiol. 283 C822-C830 (2002). 

B. Wice, D. Menton, H. Geuze, and A.L. Schwartz. Modulators of cyclic AMP metabolism induce syncytiotrophoblast formation in vitro. Exp Cell Res. 186 306-316(1990). 

Estriol is also produced by another pathway in the syncytiotrophoblast cells of the placenta DHEAS from fetal adrenal is converted to 16a-hydroxydehydroepiandrosterone sulfate in the fetal liver, followed by removal of the sulfated chain to produce 16a-hydroxy-dehydroepiandrosterone, which is then aromatized to estriol. Estriol is the predominant estrogen produced during pregnancy, and almost all of tiie estriol and estradiol produced by the placental syncytiotrophoblast enters the maternal circulation. By the 7th week of gestation, the placenta produces the majority of the estrogen in the maternal circulation. 

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