Background: Nanotechnology is a rapidly developing field. People are increasingly exposed to nanoparticle (NP)- containing consumer products, and to NP based drugs and diagnostic procedures. Nanotoxicology, however, is still in its infancy and especially little is known about routes of exposure and reproductive toxicology of NPs in man. Besides the important issue of potential NP interaction with germ cells in the testis or ovary, it will be crucial to understand NP interference with human placenta, to assess a possible risk for human embryonic and fetal development. Due to the size of NPs, being quite large compared to most “classical drugs”, NP trafficking is expected to depend much more on the specific structure of the biological barriers. Since the placenta is one of the most species- specific organs, animal data on placental NP interference will be more difficult to interpret and comparatively cheap in vitro models of the human placenta might gain more attention in preclinical testing. For analysis of NP transfer and placental toxicity in the most critical phase, the very special architecture of the early human placenta, the hypoxic condition, the bilayer of villous trophoblast, the plugging of the spiral arteries and the contribution of intrauterine glands to nutrition have to be taken into account. The first trimester placental explant culture covers at least some of these issues.
Objectives: To analyse NP- uptake in early human placenta, and it dependence on size, dose, and surface charge, and to gain insight into uptake mechanisms and possible toxic effects of different NPs.
Methods: First trimester human placental explants are obtained with permission of the local ethics committee and cultivated. NP exposure is analysed using light microscopy, fluorescence microscopy, electron microscopy, Immuno- histochemistry and biochemical tests for acute toxicity and hormone production.
Franz Lanyar Stiftung grant #350