Experimental methods to study human transplacental exposure to genotoxic agents.
Human placenta differs more than any other organ between species. This is the primary reason to develop models utilizing human tissue to study placental functions. There are no major ethical restrictions using human placenta for scientific studies. Also, the size of human placenta enables a great number of different parameters to be studied in one placenta. The most important cell types considering transplacental transfer, are the trophoblasts differentiating into syncytiotrophoblasts facing maternal circulation, and endothelial cells of fetal vessels. Primary trophoblasts are difficult to culture and do not grow in monolayer thus inhibiting studies on the polarized functions of transport. Several cell lines originating from trophoblasts have been developed, of which BeWo cells seem most useful for transport studies, because they grow in a tight monolayer. Placental tissue can also be retained as explant cultures, although the trophoblast viability is very restricted despite of culture conditions. Cotyledons of human placenta can be retained viable in an isolated organ perfusion. Perfused placental tissue stays viable longer than placental tissue in tissue culture. Although human placental perfusion is the most tedious experimental method to study placental functions, there are several good reasons to develop it further: transplacental transfer and molecular mechanisms of genotoxic compounds can be studied. Placental perfusion is the only experimental method that retains fully the structure of placenta for polarized transport. Furthermore, perfusion of placentas from mothers, who smoke, use illegal drugs or have a disease, allows studies on the impact of such factors on fetal exposure to genotoxic agents.
Vähäkangas
Kirsi
K
Department of Pharmacology and Toxicology, University of Kuopio, P.O. Box 1627, FI-70211 Kuopio, Finland. kirsi.vahakangas@uku.fi
Myllynen
Päivi
P
D002460:Cell Line; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D008431:Maternal-Fetal Exchange; D008861:Microsomes / Q000187:drug effects / Q000502:physiology; D008954:Models, Biological; D009153:Mutagens / Q000633:toxicity*; D010477:Perfusion; D010920:Placenta / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology; D011247:Pregnancy; D046509:Tissue Culture Techniques
D009153:Mutagens