Placental Specific mRNA in the Maternal Circulation Are Globally Dysregulated in Pregnancies Complicated by Fetal Growth Restriction

Abstract

There is global differential expression of placental specific mRNA in the maternal blood in pregnancies complicated by severe preterm FGR. Placental specific mRNA in maternal blood may represent a new class of biomarkers for preterm FGR.

Variable effect of maternal oral glucose load on circulating cell-free placental mRNAs

“…Only 8 of a possible 137 placenta-specific genes [2] were investigated, and interpretable levels were only available for six genes. The reason for the poor amplification of PLAC1 and PSG5 transcripts is unclear.…”

“…We selected eight genes that have been previously identified by our group as highly expressed in the placenta relative to other tissues via in silico analysis (http:// biogps.org) [2,7]: adrenomedullin (ADM), chorionic somatomammotropin hormone 1 (CSH1), high temperature requirement A serine peptidase 1 (HTRA1), pappalysin 2 (PAPPA2), placenta-specific 1 (PLAC1), pregnancy specific beta-1-glycoprotein 1 (PSG1), pregnancy specific beta-1-glycoprotein 5 (PSG5) and tachykinin 3 (TAC3). Relative quantification was determined by DCt (normalized cycle threshold (Ct) in paired fasting and 1-h post-glucose samples) using glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and b-2 microglobulin (B2M) as housekeeping genes.…”

“…A non-invasive biomarker to detect FGR would be a valuable screening test that may reduce stillbirth. Our group has previously demonstrated dysregulation of placental mRNAs in the maternal circulation in cases of FGR [2], suggesting this is a promising approach to biomarker discovery.…”

“…These transcripts represent potential non-invasive markers of placental function that could be used for prediction, diagnosis or prognosis of placental diseases such as fetal growth restriction (FGR) [2] or preeclampsia [3].…”

Noninvasive nucleic acid–based approaches to monitor placental health and predict pregnancy-related complications

“…89 Furthermore, a gene hypoxia score, defined as a sum of the relative expression of 4 hypoxia-induced mRNAs in the maternal blood (hypoxia-inducible factor-1a, hypoxiainducible factor-2a, adrenomedullin, and lactate dehydrogenase A) correlated with the degree of fetal hypoxia evaluated using fetal blood pH levels. 90 The role of miRNA changes for normotensive IUGR has not been well investigated. Several studies have detected IUGR-specific miRNA expression changes in placentae, but these differences were not detectable in plasma.…”