Fetal model

The first reports documenting ethanol-induced oxidative stress in a fetal model appeared about 20 years ago. They linked maternal ethanol intake to evidence of lipid peroxidation products in fetal rat liver (Dreosti, 1987 Dreosti and Partick,... 

Information on the transplacental transfer of americium in humans is not available directly, but the information from experiments with americium and other actinides has been used to derive biokinetic models and perform dosimetric models for the human (NCRP 1998 NRC 1996 Sikov and Kelman 1989). Studies in animals that received parenteral injections of americium have shown that absorbed americium is transferred to the fetus (Hisamatsu and Takizawa 1983 Paquet et al. 1998 Sasser at al. 1986 Schoeters et al. 1990 Weiss et al. 1980) (see Section 3.4.2.1). Limited reports indicate that241 Am may induce fetal death and teratogenic effects in rodents (Moskalev et al. 1969 Rommerein and Sikov 1986). 

The degree of exposure of the fetus to a particular substance can be best assessed in human subjects, but concerns of fetal safety have restricted the use of this approach. Moreover, clinical studies cannot elucidate the various mechanisms that contribute to transplacental transport of a particular compound. There are many structural differences between the human placenta and the placenta of other mammalian species, which complicates extrapolation of data obtained from in vivo animal models to humans [7], Thus, several ex vivo and in vitro techniques have been developed to study the placental role in drug transfer and metabolism during pregnancy and there are some excellent articles that discuss these systems in detail [7], Both isolated tissues and various cell culture techniques are currently in use and these have been summarized below. 

Some P-gp inhibitors have been tested in clinical trials (e.g., GF120918, PSC 833) [88, 89], Shortly before birth, it is often desirable to expose the fetus to anti-HIV medications to prevent HIV transmission from the mother to the fetus during delivery. Preperfusion with P-gp inhibitors increased fetal penetration of the protease inhibitor saquinavir in in vitro placental models, and it has been hypothesized that P-gp may be responsible for limiting fetal exposure to HIV protease inhibitors, methadone, anthracyclines, and taxanes [90-93],... 

Other cell lines used in permeability studies include the T84 human colonic adenocarcinoma colonic crypt cell model. This line has a reduced carrier expression, secrets mucus, and has very high resistance [31, 32], The IEC cell line is a rat fetal intestinal epithelium cell with higher permeabilities than Caco-2 cells [33], LLC PKi is a pig kidney epithelial cell line with low expression of efflux systems, but expression systems for transport proteins [32], 2/4/A1 cells are a conditionally immortalized rat fetal intestinal epithelium line with crypt cell-like morphology and temperature-sensitive differentiation [34], They form differentiated monolayers with tight junctions, increased brush border enzymes when grown on extracellular matrices with laminin. Transport of drugs with LP in 2/4/A1 monolayers was comparable to that in the human jejunum and up to 300 times faster than that in Caco-2 monolayers. In contrast, the permeability of HP drugs was comparable in both cell lines [34],... 

Weinzweig, J., Panter, K.E., Pantaloni, M., Spangenberger, A., Harper, J.S., Lui, F., James, L.F. and Edstrom, L.E. (1999b). The fetal cleft palate II. Scarless healing after in utero repair of a congenital model, Plastic and Reconstr. Surg., 104, 1356-1364. 

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