Fetal and embryonic hemoglobins in erythroblasts of chromosomally normal and abnormal fetuses at 10-40 weeks of gestation.
OBJECTIVE
During fetal development a change in erythropoiesis from hepatic to medullary site occurs. In chromosomally abnormal fetuses this change is delayed. Hemoglobin production also undergoes developmental switches from embryonic to fetal hemoglobins in the first trimester of pregnancy. The aim of study was to determine the proportion of embryonic and fetal hemoglobins in fetal erythroblasts of chromosomally normal and abnormal fetuses at 10-40 weeks of gestation.


METHODS
Fetal blood was obtained from 93 chromosomally normal and 19 abnormal fetuses at 10-40 weeks of gestation. Fetal erythroblasts were isolated by triple density gradient centrifugation and magnetic cell sorting with CD71 antibody. Fluorescent antibodies were used to immuno-stain for zeta (zeta), epsilon (epsilon) and gamma (gamma) hemoglobin chains.


RESULTS
The percentages of the positively stained cells were calculated. In chromosomally normal fetuses the percentage of erythroblasts expressing the zeta chain was 25% at 10 weeks but this decreased exponentially with gestation to less than 1% by 17 weeks. Similarly, the percentage of cells expressing the epsilon chain decreased from 97% at 10 weeks to less than 1% by 25 weeks. In contrast, expression of the gamma chain increased from about 30% at 10 weeks to 90% by 16 weeks and decreased thereafter to 60% at 40 weeks. In the abnormal fetuses, the percentage of erythroblasts expressing the zeta chain and the epsilon chain decreased to less than 1% by 23 and 28 weeks respectively, while maximum expression of the gamma chain was at about 22 weeks.


CONCLUSIONS
In the chromosomally abnormal group the pattern of change in the expression of the various hemoglobin chains during gestation was similar to that in the normal fetuses but was delayed by three to six weeks. These findings suggest that in fetuses with chromosomal abnormalities there is a developmental delay in the switch from embryonic to fetal hemoglobin chains.
Al-Mufti
R
R
Harris Birthright Research Centre For Fetal Medicine, Denmark Hill, London, England.
Hambley
H
H
Farzaneh
F
F
Nicolaides
K H
KH
D000328:Adult; D000906:Antibodies; D015703:Antigens, CD / Q000097:blood / Q000276:immunology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000097:blood / Q000276:immunology; D002498:Centrifugation / Q000379:methods; D002869:Chromosome Aberrations; D025063:Chromosome Disorders; D004622:Embryo, Mammalian / Q000737:chemistry*; D004900:Erythroblasts / Q000378:metabolism*; D005260:Female; D005319:Fetal Hemoglobin / Q000737:chemistry / Q000378:metabolism*; D005333:Fetus / Q000737:chemistry; D006801:Humans; D018189:Immunomagnetic Separation; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011262:Pregnancy Trimester, Second; D011263:Pregnancy Trimester, Third; D011990:Receptors, Transferrin
D000906:Antibodies; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; C068126:CD71 antigen; D011990:Receptors, Transferrin; D005319:Fetal Hemoglobin