Increased placental expression and maternal serum levels of apoptosis-inducing TRAIL in recurrent miscarriage

Rull, K., Tomberg, K., Kõks, S., Männik, J., Möls, M., Sirotkina, M., Värv, S. and Laan, M. (2013) Increased placental expression and maternal serum levels of apoptosis-inducing TRAIL in recurrent miscarriage. Placenta, 34 (2). pp. 141-148.

Abstract

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.

Item Type:	Journal Article
Publisher:	Elsevier
Copyright:	© 2012 Elsevier Ltd.
URI:	http://researchrepository.murdoch.edu.au/id/eprint/51770

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