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

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 ␥-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 ␥-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: ␥-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 ␥-globin mRNA were decreased in most women after TOP, but ␥-globin

Placental mRNA in Maternal Plasma and Its Clinical Application to the Evaluation of Placental Status in a Pregnant Woman with Placenta Previa-Percreta

“…Because circulating GAPDH mRNA in cancer patients was thought to originate in apoptotic cancer cells (2,5 ), the increased concentrations of GAPDH mRNA detected may be caused by apoptosis in the placental residue in our case.…”

“…A quantitative study of plasma mRNA for ␥-globin and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) showed significantly higher concentrations in pregnant women than in nonpregnant women (2 ). These findings suggest that the quantitative analysis of placental mRNA in maternal plasma may be a useful method to monitor placental status.…”

“…ANP and BNP share potent diuretic, natriuretic, and vascular smooth-muscle-relaxing effects and interact with the hormonal and nervous systems (1)(2)(3). Stimulation by hemodynamic overload, as well as by several neuroendocrine (including ␣-adrenergic agonists, angiotensin II, endothelins, and vasopressin) and immunologic agents and by growth factors, modulates the production of CNHs by the human heart (1, 2 ).…”

“…The clinical relevance of measurement of BNP and its related peptides as diagnostic tools and prognostic markers in patients with cardiovascular diseases has been confirmed recently (2,3 ). To achieve correct interpretation of serial test results that are collected for follow-up or for tailored treatment of heart failure patients, several studies (4 -8 ) recently evaluated the biological variation of BNP and its related peptides in both healthy persons and cardiac patients.…”

“…In that study, only the group of patients treated with the beta-blocker agent carvedilol, who responded on average with a decrease of only 38% in plasma BNP, showed a clinical improvement (9 ). Furthermore, several studies have demonstrated that cardiovascular risk (mortality or major cardiovascular events) increases continuously and progressively throughout the whole range of BNP concentrations in patients with cardiovascular diseases (i.e., an absolute threshold for risk cannot be determined) (2 ).…”