Plasma gamma-globin gene expression suggests that fetal hematopoietic cells contribute to the pool of circulating cell-free fetal nucleic acids during pregnancy

Clin Chem. 2004 Apr;50(4):689-93. doi: 10.1373/clinchem.2003.030064.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Female
  • Fetal Blood / cytology*
  • Globins / biosynthesis*
  • Globins / genetics
  • Hematopoietic Stem Cells / metabolism*
  • Humans
  • Male
  • Mothers
  • Nucleic Acids / blood*
  • Pregnancy / blood*
  • Pregnancy Trimesters
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / blood
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Nucleic Acids
  • RNA, Messenger
  • Globins