The long term objective of the proposed research program is to elucidate the physiologic mechanisms that regulate the uptake of water by the conceptus and to apply these principles to two human diseases, polyhydramnios and hydrops fetalis. Uptake of water by the conceptus can occur by way of the placenta and by way of direct exchange between amniotic fluid and maternal plasma, or between allantoic fluid and maternal plasma, depending on species. The quantitative significance of direct exchange via the latter two paths is not known. The research plan, therefore, first outlines an experimental procedure for determining the magnitude of extraplacental exchange of water and solutes and second presents a theoretic and experimental program for determining the exchange characteristics of extraplacental sites that are found. With these additions to the already existing knowledge of placental exchange, the investigators will have a complete description of maternofetal exchange of water and osmotically significant solutes. The physicochemical abnormalities that constitute the basis of polyhydramnios or hydrops fetalis are unknown and could be any one of several theoretic possibilities. The research plan distinguishes a transient state and a steady state in these diseases processes and shows that neglect of this distinction may lead to paradoxical interpretations of experimental findings. The plan then presents a systematic analysis for identification of the underlying abnormality. An existing animal model for the study of polyhydramnios and hydrops fetalis is available. Several additional models for the study of these diseases are proposed.
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