Plasma mRNA concentrations of placenta-specific 1 (PLAC1) and pregnancy associated plasma protein A (PAPP-A) are higher in early-onset than late-onset pre-eclampsia.

AIM: Some mRNA concentrations are observed to increase in the maternal circulation in association with pre-eclampsia, including placenta-specific 1 (PLAC1) and pregnancy associated plasma protein A (PAPP-A), which were previously proposed as predictive markers for pre-eclampsia. Here, we investigated their concentrations in early-onset and late-onset pre-eclampsia maternal plasma to determine whether different mechanisms are involved in these two forms of the disorder. MATERIAL AND METHODS: Peripheral blood and placental samples were collected from patients with pre-eclampsia. RNA was extracted and levels of PLAC1 and PAPP-A mRNAs were determined using real-time quantitative PCR. RESULTS: PLAC1 and PAPP-A mRNA levels were significantly increased in plasma from pregnant women with pre-eclampsia compared with those from healthy pregnant women. The median concentration of PLAC1 was 5.5 times higher (P<0.01) and that of PAPP-A was 5.1 times higher (P<0.01) in early-onset than in late-onset pre-eclampsia. The expression of these mRNAs in the placenta showed no significant difference in early-onset pre-eclampsia, late-onset pre-eclampsia and healthy pregnant women. CONCLUSION: These findings suggest that the concentration of mRNAs in maternal plasma reflect leakage from damaged villus cells rather than expression levels in the placenta. Injury to chorionic villus cells might be more severe in early-onset pre-eclampsia than in late-onset pre-eclampsia.

No correlation between the number of fetal nucleated cells and the amount of cell-free fetal DNA in maternal circulation either before or after delivery.

OBJECTIVES: We have determined the number of fetal nucleated cells and the concentration of cell-free fetal DNA in parallel in the same maternal blood samples either before or after delivery, and studied the relationship between these two. METHODS: Venous blood samples were taken at four points around delivery from ten women who had singleton male fetus with informed consent. The number of fetal nucleated cells having a Y chromosome specific signal treated by two-color fluorescence in situ hybridization technique was counted using maternal whole blood. The concentration of sex-determining region Y gene sequence was determined using real-time quantitative PCR. RESULTS: The number of fetal nucleated cells decreased after delivery, and some fetal cells were present 1 month after delivery. While cell-free fetal DNA decreased rapidly after delivery and became undetectable 1 day after delivery in eight out of ten cases. The number of fetal nucleated cells did not correlate with the concentration of cell-free fetal DNA in maternal circulation. CONCLUSION: The present study demonstrates that cell-free fetal DNA disappears very rapidly after delivery and fetal nucleated cells remain longer in maternal circulation, and that there is no correlation between these two either before or after delivery.

Cell-free mRNA concentrations of CRH, PLAC1, and selectin-P are increased in the plasma of pregnant women with preeclampsia.

OBJECTIVE: To compare mRNA concentrations of corticotrophin-releasing hormone (CRH), placenta specific-1 (PLAC1), and selectin-P in preeclamptic and normal pregnancies. METHODS: Peripheral blood samples were obtained from 43 pregnant women with preeclampsia and 41 control subjects. Plasma was harvested from samples and RNA extracted. Plasma RNA was analyzed using reverse transcription polymerase chain reaction (PCR) assay. Median concentrations of CRH, PLAC1, and selectin-P mRNA in plasma were compared, to assess possible differences in distribution. Data were also stratified and compared according to clinical severity of preeclampsia. Finally, CRH, PLAC1, and selectin-P were plotted against quantitative distributions of blood pressure and proteinuria. RESULTS: All markers were differently distributed between cases and controls. Median values in subgroups correlated with severity of preeclampsia. All markers correlated with both. Selectin-P was identified as the marker with the highest degree of correlation. No correlation was found between any markers in the control group and proteinuria or blood pressure. CONCLUSION: CRH, PLAC1, and selectin-P are distributed differently in preeclampsia cases compared to controls and correlate with signs of preeclampsia.

Increased plasma mRNAs of placenta-specific 1 (PLAC1) and glial cells-missing 1 (GCM1) in mothers with pre-eclampsia.

In this study we have investigated whether quantitative analysis of placental mRNAs in maternal plasma provides a way to monitor placental status. We measured plasma concentrations of human chorionic gonadotropin beta-subunit (betahCG) and human placental lactogen (hPL) mRNAs as previously reported mRNAs and pregnancy associated plasma protein A (PAPP-A), placenta-specific 1 (PLAC1) and glial cells-missing 1 (GCM1) mRNAs, which have not been measured during the course of normal pregnancy. Firstly, peripheral blood was obtained at various times from healthy pregnant women to clarify the time course of placental mRNAs. Secondly, blood was obtained from women with pre-eclampsia and gestational age-matched controls to examine whether placental mRNAs change in pre-eclampsia. Plasma was separated from these samples for extraction of RNA, followed by reverse transcription polymerse chain reaction analysis. Median concentrations of PLAC1 and GCM1 mRNA in plasma of pre-eclamptic subjects respectively were 1625 and 2141 copies/ml, significantly higher than 195 and 881 copies/ml, the values for controls (Mann-Whitney test, p<0.001). No significant difference was seen in hPL, betahCG, or PAPP-A mRNA concentration between pre-eclamptic and control groups. Plasma PLAC1 and GCM1 mRNAs appear promising as noninvasively measurable molecular markers for pre-eclampsia.