Maternal-fetal iron transfer across the placenta is vital for fetal growth and is adversely affected by maternal iron deficiency. The most common hematologic and nutritional disease of pregnancy is iron deficiency or depletion, which is present in 30 to 90% of pregnant women (Fairbanks and Beutler, 1977). The subcellular route of placental iron transport is not known, but is a requisite for understanding maternal-fetal iron metabolism. In this study we propose to correlate the ultrastructural distribution of inherent and administered iron with kinetic studies of iron uptake in the hemomonochorial placenta of the guinea pig. The anatomic distribution of non-heme ferric and ferrous iron deposits (including transferrin and ferritin iron) will be described and semiquantitated after staining with acid ferrocyanide and ferricyanide. The staining will be evaluated in the 1st, 2nd and 3rd trimester placentas of guinea pigs with normal iron repletion; and in the third trimester placentas of iron deficient guinea pigs. During the third trimester of normal and iron deficient animals radioiron will be administered intravenously as FeCl3 or as heat damaged erythrocytes to evaluate placental uptake from maternal serum and storage iron pools respectively. Movement of radioiron into the placenta and fetus will be documented using a small animal whole body scintillation detector, and the data correlated with ultrastructural, cytochemical and radioautographic examination of placental tissue. These results will also be compared to the placental distribution of ferritin, apoferritin, transferrin and apotransferrin using ultrastructural immunocytochemical methods. The success of these methods in this laboratory has resulted in several publications localizing ferritin, transferrin and absorbed iron in a variety of tissues. The proposed study will extend this information to the placenta and provide information about the subcellular location, mobility and accessibility of specific iron deposits.