Limited expression of Fas and Fas ligand in fetal nucleated erythrocytes isolated from first trimester maternal blood.
OBJECTIVE
Intact fetal cells isolated from maternal blood can be used for non-invasive gender determination and genetic diagnosis. Recent studies demonstrating a large amount of cell-free fetal DNA in maternal plasma suggest that the circulating fetal DNA may result from fetal cells undergoing apoptosis. In the present study we evaluated the potential role of Fas and Fas ligand (FasL) cell surface expression with respect to apoptosis induction in fetal cells isolated from maternal blood.


METHODS
We flow sorted candidate fetal cells that were gamma chain-positive and Fas- or FasL-positive or -negative, and subsequently analysed them by fluorescence in situ hybridization (FISH) analysis using X and Y chromosome-specific probes.


RESULTS
Among all gamma hemoglobin-positive cells, there was a significant difference in the percent of cells expressing Fas versus FasL (4.4 and 12.3, respectively). We found no significant correlation between the total number of fetal nucleated red blood cells (NRBCs) and gestational age or the presence of Fas- and FasL-positive cells. From approximately 7 ml of maternal peripheral blood, most of the confirmed fetal (XY) cells were found in the Fas- and FasL-negative sorted population; the average numbers were 12.8 and 15.7, respectively.


CONCLUSIONS
We conclude that fetal NRBCs express FasL more than Fas, although most fetal NRBCs in first trimester maternal blood samples do not express Fas or FasL. This suggests the absence of a functional Fas/FasL apoptotic system in fetal NRBCs, and that programmed cell death in these cells, which may lead to circulating fetal DNA in maternal plasma, probably occurs by another pathway.
Sohda
Satoshi
S
Division of Genetics, Department of Pediatrics, New England Medical Center, Tufts University School of Medicine, Boston, MA 02111, USA.
Samura
Osamu
O
Johnson
Kirby L
KL
Falco
Vincent M
VM
Elmes
R Sarah
RS
Bianchi
Diana W
DW
D000328:Adult; D017209:Apoptosis / Q000502:physiology; D004247:DNA / Q000032:analysis; D053938:DNA Fragmentation; D004900:Erythroblasts / Q000378:metabolism*; D053222:Fas Ligand Protein; D005260:Female; D005312:Fetal Blood / Q000166:cytology* / Q000378:metabolism; D005331:Fetomaternal Transfusion; D005434:Flow Cytometry; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008562:Membrane Glycoproteins / Q000378:metabolism*; D011247:Pregnancy / Q000097:blood*; D011261:Pregnancy Trimester, First; D019014:fas Receptor / Q000378:metabolism*
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019014:fas Receptor; D004247:DNA