We have identified an RNA-directed DNA polymerase in human placental extracts. The aims of this proposal are the biochemical and immunological characterization of this RNA-directed DNA polymerase (RDDP) in human placentas and the determination of its function in placental and fetal development. In more than 80 per cent of the placentas, this enzyme activity was found after isopycnic centrifugation in sucrose at 1.15-1.17 g/ml, the density of type C-retroviruses. By several biochemical criteria, the RDDP activity appears to be of viral rather than cellular origin. However, convincing proof that the RDDP is a unique, viral polymerase requires the purification of the placental RDDP and the comparision of its antigenic properties with other cellular DNA polymerases. The experimental approach will involve: 1. Purification of the human placental RNA-directed DNA polymerase and the celluar DNA polymerases alpha, beta, and gamma. 2. Establishment of its antigenic relatedness to cellular and viral polymerases. 3. Development of a radioimmunoassay for the detection of RDDP. 4. Use of this assay to measure activity throughout placental development. 5. Use of this assay to detect Anti-RDDP activity in sera from women at different stages of pregnancy and from women with histories of spontaneous abortion. This study will determine whether spontaneous abortions may be correlated with anti-RDDP activity in maternal sera. The data generated is expected not only to give information about polymerase function in placental development but to be of diagnostic value in monitoring intrauterine fetal development and in establishing a cause for spontaneous abortions.