Table 1. Summary of microarray studies in preeclampsia.
| Author | Group | Mother age | Gest. age (wks) | BMI | MOD | Sampling | Microarray | Finding | Hot genes | Pathways |
|---|---|---|---|---|---|---|---|---|---|---|
| Jarvenpaa 2007 Finland | 2 PE + IUGR 3 ctrl | 21.5 27.7 |
35.7 38.5 |
20 27.3 |
Cs without labor | Not described | Affymetrix Human U133 plus 2.0 | 4 genes up 9 genes down | Up: EPAS1, FLT1, SIGLEC10, ANG4 Down: ECGF1, JAG1, Palladin, COL18A1, TNFSF12, VEGF, ANPEP, PDGFA, SERPIN12 | Angiogenesis |
| Centlow 2008 Sweden | 10 PE 5 PE +notch 5 notch 15 ctrl | 28.5±2.9 32.4±4.3 31.8±5.8 31±3.3 | 37.7±2.3 35.0±4.1 38.9±3.1 40.0±1.4 | Cs/vag. | Villous tissue from central part of placenta, frozen on dry ice and stored at -80°C. | Operon v 2.1 human 70 mer oligo set | 30 genes were altered in at least one fold between-group comparison. | Up: Hbα2, Hbγ and Hbβ in PE vs. ctrl. | Potent toxins: endothelial damage, inflammation | |
| Toft 2008 Norway | 10 PE 8 SGA 10 PE+ SGA | 30.3±5.4 34.4±5.0 30.3±4.9 | 34.2±2.5 34.5±3.8 33.9±2.0 | Cs | Tangentially dissection from the maternal side close to umbilical cord, stored at -80°C. | Affymetrix HG U133 plus 2.0 | No difference between study groups. | qPCR: FLT1 and ENG are up regulated in PE+SGA group | Angiogenesis | |
| Enquobahrie 2008 USA | 18 PE 18 ctrl | 32.6 30.0 | 35.8 38.9 | 27.0 25.3 | 10 Cs 7 Cs | Pooled of 4 samples from maternal side, stored at -80°C. | Operon Human genome array ready oligo set | 1164 genes altered in PE vs. ctrl. 58 genes (56 up and 2 down regulated) had an absolute change ≥1.5. | Up: LEP, FLT1, PCDHA3, CYP11A, F2R, IL9, FCGR2B, CDO1, VGLL1, EBI3, INSL4, BCL6,INHA Down: MGC1132, NR4A2 | Reproductive physiology, immune response, cytokines, cell cycle |
| Winn 2009 USA Denmark | 12 PE 11 PTL | 30.7±9.1 30.2±7.1 | 32.1±3.3 31.0±4.6 | 6 Cs/10 labored 2 Cs/11 labored | Basal plate, Snap frozen. | Affymetrix HG-U133A / HG-U133B | 55 genes differentially expressed. | Up: FLT1, LEP, CRH, SIGLEC6, PAPPA2, INHA, ENG, HTRA1 | Lipid metabolism, angiogenesis | |
| Sitras 2009 Norway | 16 PE severe PE 21 ctrl | 30.5±5.2 30.2±4.8 | 34.0±3.6 39.6±1.3 | 25.9±4.8 24.8±5.3 | 11 Cs 8 Cs | Chorionic tissue, 2 cm beside umbilical cord middle layer of placenta, stored at -80°C. | Applied Biosystems Human genome survey microarray v2.0 | 213 genes up and 82 down in PE vs. ctrl. 36 up and 132 down in early- vs. late onset of PE. | Up: LEP, FLT1, FLT4, β-hCG, ENG, LAEVERIN, BCL6, INHA, MMP14, PAPPA2 Down: PDGFD | PE vs. ctrl: Angiogenesis, Oxidative stress, inflammation early vs. late: endothelial signaling |
| Founds 2009 USA (CVS) | 4 PE 8 ctrl | 36.5±0.6 38.1±3.1 | 11.4±0.7 11.3±0.6 | 29.9±4.2 24.5±4.0 | Cs/vag. | Chorionic villous sample at 10-12 wks. | Affymetrix HG-U133 Plus 2.0 Gene Chip | 5 up and 31 down in 1st trimester in PE vs. ctrl. | Up: CCK, CTGA2 Down: FSTL3, MMP12, LAIR2, S100A8 | Inflammation, immune regulation, cell motility |
| Lee 2010 Korea | 13 PE severe 13 ctrl | 31.85±3.93 33.08± 4.65 | 35.93± 0.9 38.48±0.56 | Cs without labor | Central area, stored at -80°C. Pooled RNA. | Agilent Human 4X44K | 121 up and 294 down in PE vs. ctrl. | Up: CXCR6, CXCL3, OSM, LEP, FLT1, VEGFA,SMOX, CYP26A, EGLN3, LDHA, CRY2L1 | Angiogenesis | |
| Hoegh 2010 Denmark | 11 PE 18 ctrl | Cs/vag. | Maternal side, center of cotyledons, stored differently, Pooled RNA. | Affymetrix HG-U133A Gene Chip | 12 up and 9 down in PE vs. ctrl. | Bradykinin B1 receptor, 14-3-3, INHBA, LEP | Placentation, oxidative stress, inflammation | |||
| Várkony 2011 Hungary | 6 PE 6 PE+ HELLP 5 ctrl preterm 5 ctrl term | 34.3 28.7 31.6 30.8 | 32.4 30.7 31.0 38.9 | 24.3 23.7 23.4 26.7 | Cs | Villous tissue from central cotyledons close to umbilical cord, stored at -80°C. | Agilent 44K whole human genome oligo | 181 altered in preterm vs. term, 350 in PE vs. ctrl and 554 in HELLP vs. ctrl. | Up: LEP, CGB, TREM1, LHB, SIGLEC6, PAPPA2 Down: KRT81, OPRK1 | Multicellular structure, differentiation neuroactive ligand- receptor interaction |
| Tsai 2011 USA | 23 PE 37 ctrl | 33.6±3.7 37.6±1.93 | Induc-tion of labor | Fetal side, 5 cm from umbilical cord, in liquid nitrogen | Illumina Human6- v2 BeadArray | 128 altered in PE vs. ctrl. | ENG, PAPPA2, RDH13, INHA, LEP, FLT1, SIAE, SIGLEC6 | Immune response | ||
| Chang 2011 Taiwan | 13 PE 10 ctrl 7 PE super-impose | 28.1±1.4 33.2±1.6 33.5±1.9 | 33.5±0.9 38.8±1.0 34.2±1.2 | Not descri-bed | Maternal side, stored at -80°C. | Human 15K chips | Up: HSPA1B, LIMS1, PLAGL1, TRIM31, PPP2R2C Down: RNF128, ADM, ARFIP1 | Development, apoptosis, cell death | ||
| Kang 2011 Korea | 16 PE 17 ctrl | 31.7±3.9 33.1±4.2 | 36.1±2.4 39.0±0.9 | Cs without labor | Chorionic tissue, near umbilical cord, in liquid nitrogen. | GE healthcare Human whole genome bioarrays | 132 altered, in PE vs. ctrl. | UP: FLT1, LEP ITGA5, EBI3 SIGLEC6, HTRA1 | Proliferation, differentiationimmune, biosynthesis, transport of lipid or protein | |
| Nishizawa 2011 Japan | 8 PE severe 8 ctrl 8 FGR | 31.0±4.7 31.5±6.5 31.4±3.7 | 34.4±1.8 38.1±0.8 37.3±1.0 | 21.7±3.7 21.4±2.3 19.9±1.9 | Cs without labor | Sections of placental villi between the basal and chorionic plates, in liquid nitrogen. | Affymetrix Human Exon 1.0 ST Array | 94 up and 88 down at least 1.5 fold in PE vs. ctrl. 30 up and 32 down of these in FGR. | Up: INHBA, INHA, FLRG, BCL6, LEP, UP:PAPPA2, FLT1, ENG, CGB, CRH Down: GSTA3 | p53 targets, cell growth, differentiation |
| Mayor-Lynn 2011 USA | 7 PE 7 PTL 7 ctrl | 23.8(20-26) 28.3(22-35) 30(21-38) | 35 (31-39) 28 (24-33) 38 (37-39) | 38.2 30.8 37.5 | Cs | Villous tissue. | Illumina HumanRef-12 v3 Expression BeadChip | 120 altered in PE and PTL compared to ctrl. | CRH,SOCS1,MMP1, MMP9, ADAM17, ADAM30, TIMP3, STC2, CRHBP, EDN2 | Inflammation, cell cycle, cell-to-cell signaling, Embryonic development |
| Junus 2012 Sweden | Early 8 PE 4 ctrl late: 7 PE 6 ctrl | 31.5±5.0 34.0± 4.5 30.0±11.5 24±4.5 | 29.3±3.0 24.4±1.6 39.9±1.9 40.2±2.2 | 8 Cs vag. 1 Cs 2 Cs | Central part of placenta stored at -80°C. | Operon v 2.1 human 70-mer oligo set | 88 up and 108 down in early- vs. late onset. | Down in early: ACVRL 1, EGFL7, ROBO4, IDO 1 | Angiogenesis, cell motility, oxygen transport | |
| Meng 2012 China | 6 PE 6 ctrl | 26.0±4.3 28.5±1.9 | 36.4±0.9 39.0±0.7 | Cs without labor | Sections from maternal face of the placenta Stored at -80°C | Illumina HumanHT-12 V4 BeadChip | 483 up and 456 down at least 2 fold in PE vs. ctrl. | Up: BTNL9. HMBS. ULBP1, CHRNA1, RMRP Down: INSL6, CXCL9, TMCC1, PAGE2 | Cellular function and development, cell signaling, lipid metabolism | |
| Lapaire 2012 Switzerland | 9 PE severe 7 ctrl | 36.8(22-43) 35.1(33-37) | 34.6 (33-39) 38.6 (38-41) | 26.3 (30-34) 21.1 (19-37) | Cs Cs | Villous tissue, stored at -80°C. | Affymetrix GeneChip Human 1.0 ST Arrays | 896 differentially expressed. | Up: βhCG, HTRA4, CRHBP, LHB, QPCT, CD97, MMP19, ADAM2, INHBC Down: CCL3, NOX4, VCAM1, FOSB, CX3CR1 | Riboflavin metabolism, leukocyte extravasation, NF-κB and chemokine signaling |
Cs: Cesarean section; vag: vaginal delivery; PTL: preterm labor; PE: preeclampsia; HELLP: haemolysis, elevated liver enzymes and low platelets; SGA: small for gestational age; BMI: body mass index; MOD: mode of delivery; wks: weeks; ctrl: control; FDR: false discovery rate; IUGR: intrauterine growth restriction; FGR: fetal growth restriction; Up: upregulted; Down: downregulated.