| Increased placental expression and maternal serum levels of apoptosis-inducing TRAIL in recurrent miscarriage - |
| INTRODUCTION:Recurrent miscarriage (RM; ?3 consecutive pregnancy losses) occurs in 1-3% of fertile couples. No biomarkers with high predictive value of threatening miscarriage have been identified. We aimed to profile whole-genome differential gene expression in RM placental tissue, and to determine the protein levels of identified loci in maternal sera in early pregnancy.METHODS:GeneChips (Affymetrix(®)) were used for discovery and Taqman RT-qPCR assays for replication of mRNA expression in placentas from RM cases (n = 13) compared to uncomplicated pregnancies matched for gestational age (n = 23). Concentrations of soluble TRAIL (sTRAIL) and calprotectin in maternal serum in normal first trimester (n = 35) and failed pregnancies (early miscarriage, n = 18, late miscarriage, n = 4; tubal pregnancy, n = 11) were determined using ELISA.RESULTS:In RM placentas 30 differentially expressed (with nominal P-value < 0.05) transcripts were identified. Significantly increased placental mRNA expression of TNF-related apoptosis-inducing ligand (TRAIL; P = 1.4 × 10(-3); fold-change 1.68) and S100A8 (P = 7.9 × 10(-4); fold-change 2.56) encoding for inflammatory marker calprotectin (S100A8/A9) was confirmed by RT-qPCR. When compared to normal first trimester pregnancy (sTRAIL 16.1 ± 1.6 pg/ml), significantly higher maternal serum concentration of sTRAIL was detected at the RM event (33.6 ± 4.3 pg/ml, P = 0.00027), and in pregnant women, who developed an unpredicted miscarriage 2-50 days after prospective serum sampling (28.5 ± 4.4 pg/ml, P = 0.039). Women with tubal pregnancy also exhibited elevated sTRAIL (30.5 ± 3.9 pg/ml, P = 0.035). Maternal serum levels of calprotectin were neither diagnostic nor prognostic to early pregnancy failures (P > 0.05).CONCLUSIONS:The study indicated of sTRAIL as a potential predictive biomarker in maternal serum for early pregnancy complications. |
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10 gene arrays, 6 in control group and 4 in cases
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| Sample ID | !Sample Title | Group | Tissue type |
|---|---|---|---|
| GSM558664 | elective termination, 8 weeks, 1 | uncomplicated pregnancy | placenta |
| GSM558665 | elective termination, 8 weeks, 2 | uncomplicated pregnancy | placenta |
| GSM558666 | elective termination, 8 weeks, 3 | uncomplicated pregnancy | placenta |
| GSM558667 | elective termination, 4 weeks | uncomplicated pregnancy | placenta |
| GSM558668 | elective termination, 11 weeks | uncomplicated pregnancy | placenta |
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| Sample ID | !Sample Title | Group | Tissue type |
|---|---|---|---|
| GSM558664 | elective termination, 8 weeks, 1 |
uncomplicated pregnancy |
placenta |
| GSM558665 | elective termination, 8 weeks, 2 |
uncomplicated pregnancy |
placenta |
| GSM558666 | elective termination, 8 weeks, 3 |
uncomplicated pregnancy |
placenta |
| GSM558667 | elective termination, 4 weeks |
uncomplicated pregnancy |
placenta |
| GSM558668 | elective termination, 11 weeks |
uncomplicated pregnancy |
placenta |
| GSM558669 | elective termination, 13 weeks |
uncomplicated pregnancy |
placenta |
| GSM558670 | recurrent miscarriage, 14.6 weeks |
recurrent miscarriage |
placenta |
| GSM558671 | recurrent miscarriage, 6.6 weeks, 1 |
recurrent miscarriage |
placenta |
| GSM558672 | recurrent miscarriage, 6.6 weeks, 2 |
recurrent miscarriage |
placenta |
| GSM558673 | recurrent miscarriage, 8 weeks |
recurrent miscarriage |
placenta |
| Name | ||
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