PLAC1 mRNA levels in maternal blood at induction of labor correlate negatively with induction-delivery interval.

OBJECTIVE: This study was conducted to determine whether, in low risk women having labor induced using prostaglandin gel (dinoprostone gel), there is a relationship between the concentration of mRNA for the PLAC1 gene (a trophoblast-specific gene) in maternal blood and the time elapsed between the first gel administration and spontaneous delivery. STUDY DESIGN: Blood was collected from 49 selected women at 40.2-41.4 weeks' gestation. Total RNA was extracted by means of an ABI Prism 6100 nucleic acid Prep Station and quantitative real-time PCR analysis was performed by use of a PE Applied Biosystems 5700 Sequence Detection System. Sequence data were obtained from the Genebank Sequence Database. To determine the amount of cDNA, the PLAC1 locus was used. RESULTS: Thirty women (61.2%) had a spontaneous delivery. A caesarean section, either for fetal dystocia or fetal distress, was performed in 19 (38.8%). The crude delivery rates of the women who ended up with a spontaneous delivery were 30% at 24 h and 43% at 48 h. Women (n=19) with a blood concentration of logPLAC1 mRNA>or=2.00 displayed a median time to delivery of 23.50h, (95% CI: 13.13-33.87) while those with a logPLAC1 mRNA<2.00 (n=30) had a median time of 54 h. (95% CI: 37.86-70.14; p=0.0043, log-rank test). By means of multivariate analysis, quantitative Bishop score (from 2 to 7) at the time of the first gel administration and logPLAC1 mRNA>or=2.00 were associated with a higher rate of delivery per unit of time with an odds ratio of 1.35 (95% CI: 1.07-1.71) and 3.48 (95% CI: 1.55-7.80), respectively. CONCLUSIONS: In induced term pregnancies, PLAC1 mRNA in maternal blood at the beginning of the treatment correlates with the time elapsed before delivery. This evidence demonstrates that the fetomaternal trafficking of nucleic acids is more consistent when the labor is about to begin.

PLAC1 mRNA in maternal blood correlates with Doppler waveform in uterine arteries in normal pregnancies at the second and third trimester.

Doppler analysis of the uterine arteries is currently used for pre-eclampsia (PE) screening. PLAC1 is a trophoblast-specific gene, and it is known that in normal pregnancies, trophoblastic cells are released into the maternal circulation, where specific trophoblastic mRNA can be detected. In PE, as in women who eventually develop PE, an abnormal passage of fetal and placental cells is also present. In this study, we aimed to verify whether, in normal pregnancies, Doppler waveform of the uterine arteries correlates with PLAC1 mRNA concentrations. Thirteen cases of normal pregnancies at 37 weeks' gestation (23-41) were enrolled in the study. PLAC1 mRNA was extracted from 2 mL of blood by ABI PRISM 6100 nucleic acid Prep Station (Applied Biosystems, Foster City, CA) and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis was performed by a PE 5700 Sequence detection system. Bulk RNA from normal placental tissue was used as the reference curve, and the amount of PLAC1 mRNA in the study samples was then expressed as the "relative amount" of weight of placental tissue (ng/mL). The uterine arterial mean resistance index (RI) and presence/absence of a dicrote waveform were calculated by using a 5 MHz transabdominal probe (Tecnos, ESAOTE) at the uterine cervico-corporal junction. Doppler measurement was performed on the same day as blood collection. The median of the means of uterine arterial RI was 0.52 (0.39-0.68). RI of uterine arteries and PLAC1 mRNA were significantly correlated in a log-linear regression (R(2) = 0.483, P = 0.024). Our data support that in normal pregnancy, the passage of trophoblast material into the maternal circulation is correlated with the quantitative measurement of uterine hemodynamics.

Evidence of genetic underexpression in chorionic villi samples of euploid fetuses with increased nuchal translucency at 10-11 weeks' gestation.

OBJECTIVE: To retrospectively investigate whether the genetic profile from chorionic villous sampling (CVS) found in euploid fetuses with increased NT differs from matched controls. STUDY DESIGN: We employed cDNA microarray technology to characterize and compare the gene expression profile of chorionic villous tissues (which encompass the trophoblast and inner mesenchymal core) belonging to four singleton male fetuses with increased NT at 10-11 weeks' gestation. A pool of four normal chorionic villous tissues belonging to four respective fetuses, matched for gestational age and gender, was used as controls. RESULTS: In euploid fetuses, we found several underexpressed genes, possibly involved in mechanisms associated with the abnormal NT thickness. All these genes are likely to belong to the mesenchymal core of the villus that originates from the extraembryonic mesoderm, and thus might be closely representative of the embryonic genetic profile. They include: (1) genes of embryonic development and differentiation such as Endothelin 3 (EDN3) and secreted frizzled-related protein 4 (SFRP4); (2) genes of the extracellular matrix (ECM) metabolism such as tissue inhibitor of metalloproteinase1 (TIMP1), and disintegrin-like and matrix metalloproteinase (MMP) (reprolysin type) with thrombospondin type 1 Motif or ADAMTS2, exostoses (multiple)-like 1 (EXTL1), heparan sulfate (HS) 6-O-sulfotransferase 1 or HS6ST1, fibronectin 1 (FN1) and Integrin Alpha 10 (ITGA10) involved in HS and proteoglycan bio-synthesis, ECM synthesis and cell-matrix adhesion; (3) genes involved in vessel formation and differentiation such as angiogenic factor (VG5Q), and in blood pressure control and muscle contraction, like Endothelin 3 or EDN3 and sarcolemma associated protein (SLMAP). Such lower expressions of the villous tissues might be related to an immature genetic profile of the embryo development as well as abnormal regulation of ECM bio-synthesis and/or improper vessel growth and blood pressure control. Also, the results partially support the theories proposed for NT enlargement such as altered composition of ECM and abnormal/delayed development of the circulatory system. CONCLUSIONS: Abnormal extraembryonic genetic expression is found at 10-11 weeks' gestation in euploid fetuses with increased NT. If both extra- and intraembryonic mesoderms express the same genetic alterations, then microarray analyses on CVS could be used to screen several mesoderm-derivate anomalies.