Biochemical evidence for cell fusion in placentas of mouse aggregation chimeras

Eight series of mouse chimeras were produced by aggregating 8-cell embryos that differed at the Gpi-1s locus, encoding glucose phosphate isomerase (GPI-1). Chimeric blastocysts (Gpi-1sa/Gpi-1sa <--> Gpi-1sb/Gpi-1sb) were transferred to pseudopregnant females, which produced only GPI-1C enzyme. Quantitative electrophoresis of GPI-1 was used to estimate the contribution of each embryo (GPI-1A and GPI-1B enzyme activity) to the fetus and placentas of 12 1/2 day chimeric conceptuses. Chimeric fetuses and placentas were identified by the presence of both GPI-1AA and GPI-1BB homodimers. The overall distribution of the percentage GPI-1A in the placentas was bimodal or U-shaped. It was positively correlated with the %GPI-1A in the fetus in most of the eight series of chimeras analyzed. In the first chimera experiment, involving seven series of chimeras, GPI-1AB heteropolymer was detected in 78/211 (37%) of the placentas. Heteropolymer was not detected in chimeric placentas with an unbalanced composition of GPI-1A and GPI-1B. The production of heteropolymer implies that GPI-1A and GPI-1B monomers are produced in the same cell and that fusion must have occurred between the two genetically distinct cell populations in the placenta. In the second experiment, samples of different regions were dissected from another series of 27 chimeric placentas and analyzed; 12 contained heteropolymer. Although GPI-1AB heteropolymer was widely distributed throughout the placenta it was detected less frequently in the outer part of the placenta. In another experiment, analysis of 34 homozygous (nonchimeric) Gpi-1sb/Gpi-1sb conceptuses transferred to homozygous Gpi-1sa/Gpi-1sa reproductive tracts revealed no evidence for fusion between maternal cells and cells of zygotic origin in the placenta. The chimera studies provide biochemical evidence for fusion between zygotic cells in the murine placenta. This presumably occurs during the formation of the syncytial trophoblast.