Yolk sac: site of developmental microheterogeneity of mouse alpha-fetoprotein.

α-Fetoprotein was observed to be synthesized in mouse fetal liver and yolk sac by incorporation of radioactive leucine into appropriate tissue cultures. Cultured fetal liver during early (Day 13.5) and late (Day 16.5) development secreted predominantly the maximally sialylated Fp5. In contrast, the yolk sac secreted a developmentally changing array of α-fetoprotein: Day 11.5 yolk sac secreted predominantly the unsialylated Fp1, at Day 13.5, the yolk sac secreted all five electrophoretic forms of α-fetoprotein, and by Day 16.5, only Fp5 was predominantly secreted, as in the fetal liver. To ascertain whether the ³H-labeled proteins that appeared in the regions of α-fetoprotein on polyacrylamide gels represented α-fetoprotein, immunoprecipitations with anti-α-fetoprotein were carried out. After the immunoprecipitations, radioactivity in the regions of marker α-fetoprotein on polyacrylamide gels was decreased to background levels. When sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the immunoprecipitates was performed, radioactivity peaks comigrated with marker α-fetoprotein. The undersialylated α-fetoprotein forms do not appear to arise by loss of sialic acid following secretion as determined by mixing experiments of yolk sac and fetal liver in culture. The contribution of α-fetoprotein synthesized and secreted by fetal liver and yolk sac at Days 13.5 and 16.5 of development was compared. Day 13.5 yolk sac incorporated 6.7 times as much radioactivity into secreted α-fetoprotein as did fetal liver at this time. These results suggest that during early development, the yolk sac is primarily responsible for the synthesis and secretion of the undersialylated forms of α-fetoprotein. In addition to the microheterogeneity of α-fetoprotein attributed to the number of sialic acid residues attached to the glycoprotein, there appeared to be other changes in α-fetoprotein: Fp5 synthesized from fetal liver migrated slightly faster on polyacrylamide gels than that from yolk sac.