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Clinical Chemistry 50: 689-693, 2004; 10.1373/clinchem.2003.030064
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Right arrow Molecular Diagnostics and Genetics
(Clinical Chemistry. 2004;50:689-693.)
© 2004 American Association for Clinical Chemistry, Inc.

Molecular Diagnostics and Genetics

Plasma {gamma}-Globin Gene Expression Suggests that Fetal Hematopoietic Cells Contribute to the Pool of Circulating Cell-Free Fetal Nucleic Acids during Pregnancy

Tuangsit Wataganara1, Erik S. LeShane1, Angela Y. Chen3,1, Lynn Borgatta3, Inga Peter2, Kirby L. Johnson1 and Diana W. Bianchi1,a

1 Division of Genetics, Departments of Pediatrics, Obstetrics and Gynecology, and2 Institute of Clinical Research and Health Policy Studies, Tufts-New England Medical Center, Boston, MA.
3 Department of Obstetrics and Gynecology, Boston Medical Center, Boston, MA.

aAddress correspondence to this author at: Division of Genetics, Departments of Pediatrics, Obstetrics and Gynecology, Tufts-New England Medical Center, 750 Washington St., Box 394 Tufts-NEMC, Boston, MA 02111. Fax 617-636-1469; e-mail dbianchi{at}tufts-nemc.org.

Background: Reports of placental mRNA sequences in the plasma of pregnant women suggest that the placenta is the predominant source of cell-free fetal nucleic acids in maternal plasma during pregnancy. We developed an assay for {gamma}-globin mRNA concentrations to determine whether hematopoietic cells also contribute to the pool of fetal mRNA in maternal plasma.

Methods: Frozen paired plasma samples obtained from 40 women before and within 20 min after elective first-trimester termination of pregnancy (TOP) were analyzed. Fresh plasma samples from eight nonpregnant individuals were included as controls. Plasma {gamma}-globin mRNA was measured by use of real-time reverse transcription-PCR and analyzed with gestational age. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA was used to confirm the presence of cell-free RNA in each sample.

Results: {gamma}-Globin and GAPDH mRNA sequences were detected in every plasma sample. The concentrations of both messages were significantly increased in pregnancy (P <0.01). The concentrations of {gamma}-globin mRNA were decreased in most women after TOP, but {gamma}-globin mRNA was increased in some patients when TOP was performed later than 9 weeks of gestation.

Conclusions: {gamma}-Globin mRNA sequences can be detected and measured in fresh and frozen plasma samples. Plasma {gamma}-globin and GAPDH mRNA concentrations are affected by pregnancy. The increased posttermination {gamma}-globin mRNA concentrations seen in some patients suggest that the source of this message is fetal hematopoietic cells. Further study in pregnant women after 9 weeks of gestation is necessary to evaluate the potential of {gamma}-globin mRNA as a marker for fetomaternal hemorrhage.




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