The Concentration of Circulating Corticotropin-releasing Hormone mRNA in Maternal Plasma Is Increased in Preeclampsia

Abstract

Background: Increased fetal DNA in maternal plasma/ serum has been reported in pregnancies complicated by preeclampsia. We hypothesize that fetal RNA may also be increased in maternal plasma in preeclampsia. Methods: We developed a real-time quantitative reverse transcription-PCR assay to measure the concentration of the mRNA of the corticotropin-releasing hormone (CRH) locus. Peripheral blood samples were obtained from healthy pregnant women both before and 2 h after delivery. Peripheral blood samples were also obtained from women suffering from preeclampsia and controls matched for gestational age. Plasma was harvested from these samples, and RNA was extracted. Plasma RNA was subjected to analysis by the reverse transcription-PCR assay. Results: CRH mRNA was detected in the plasma of 10 healthy pregnant women in the third trimester. CRH mRNA was found to be cleared very rapidly after cesarean section, with no detectable signal by 2 h postpartum. Plasma CRH mRNA concentrations were 1070 and 102 copies/mL, respectively, in 12 preeclamptic women and 10 healthy pregnant women matched for gestational age (Mann-Whitney test, P <0.001). Conclusion: Plasma CRH mRNA represents a new molecular marker for preeclampsia. Maternal plasma RNA is gender-and polymorphism-independent and may allow noninvasive gene-expression profiling of an unborn fetus.

A strategy for identifying circulating placental RNA markers for fetal growth assessment

“…The increased release of ADAM12 mRNA into the plasma of IUGR with PET pregnant women may be related to increased placental ADAM12 mRNA expression in preeclamptic placental tissue, which is in agreement with previous studies on ADAM12 at the protein level (Gack et al, 2005). Moreover, increased concentrations of cellfree nucleic acids in PET has been reported in several studies (Lo et al, 1999;Zhong et al, 2001;Ng et al, 2003a;Purwosunu et al, 2007) and speculated to be associated with increased placental apoptosis in pregnancies complicated by PET .…”

“…Quantification of plasma placental RNA is not limited by the fetal gender or genotype, and allows marker development from disease-specific gene expression patterns. For example, our group has reported that circulating fetal RNA analysis could be applied for the noninvasive prenatal diagnosis of pre-eclampsia (PET) and fetal aneuploidies (Ng et al, 2003a;Ng et al, 2004;.…”

Integrative single-cell and cell-free plasma RNA transcriptomics elucidates placental cellular dynamics

“…It has been shown that the placenta is the major source of circulating cell-free fetal nucleic acids in maternal plasma (5)(6)(7). Significantly elevated levels of total cell-free DNA and selected placenta-specific RNA transcripts have also been reported in the maternal plasma of women with PE (8)(9)(10)(11), restricted fetal growth (12), and preterm birth (13)(14)(15), supporting a role for cell-free nucleic acids as a noninvasive tool for placental monitoring. Previous studies have attempted to provide a comprehensive assessment of maternal plasma nucleic acids by microarray analysis, massively parallel transcriptomic, or methylomic sequencing (16)(17)(18)(19)(20)(21)(22).…”

Intrauterine Diagnosis of Genodermatoses

“…Another advantage is the fact that fetal DNA can be discovered in maternal blood as early as the fourth week of gestation, and reliably after the seventh week of gestation [54]. In addition to fetal DNA, fetal mRNA and microRNAs also exist in maternal plasma, and they can provide knowledge about fetal gene expression, mirroring different physiological conditions [48,[55][56][57].…”