MOLECULAR SIZE SELECTIVITY OF IMMATURE PLACENTA

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The long-term objective is to obtain quantitative information on the permeability of the immature placenta in animals with hemochorial placentas. The expectation is that the results on immature placentas can be extrapolated to the early human placenta, like the results on mature hemochorial placentas could be extrapolated to the mature human placenta. The first hypothesis to be tested is that the immature placenta evolves through stages of changing permeability and changing molecular selectivity. The second hypothesis is that the permselectivities of the various types of hemochorial placentas are strongly related to stage of conceptual development, possibly more so than to differences in histological structure. Specific aims are to determine the permeability of the early placenta to hydrophilic, metabolically inert, charged and non-charged probes with molecular radii from 0.2 to 1.22 nanometers. Placentas of 0.3, 0.4, 0.5, 0.6, and 0.7 gestational age will be studied in the guinea pig, rabbit and rat. The hemomonochorial human placenta is structurally closely related to the guinea pig placenta. Nevertheless, its molecular size selectivity is more closely mirrored in the hemodichorial placenta of the rabbit and the hemotrichorial placenta of the rat than in the placenta of the guinea pig. For these reasons all 3 hemochorial species will be studied. The rules that govern diffusional exchange apply to all materials traversing the placental barrier. For this reason, the study of diffusional transfer provides information on more materials at lesser cost than the study of carrier mediated transfers. The study of the permeability of the early placenta will help to predict the exposure levels of the early human embryo to therapeutic xenobiotics such as antiviral/anti HIV agents and teratogens because preliminary data indicate that it is far less permeable than its mature counterpart.