Genome-wide expression profiling at maternal-fetal interface in case of recurrent miscarriage (RM)

ABSTRACT: Maternal-fetal interface plays a crucial role to ensure a successful pregnancy. RM (≥3 consecutive pregnancy losses) occurring in 1-3% of fertile couples has a heterogeneous background with contribution from both genetic and environmental factors. As several physiological processes are affected in the pathogenesis of RM, it serves as a good model to study the processes at the maternal-fetal interface. We aimed to map differentially expressed genes and pathways affected in case of RM. Affymetrix® GeneChip® HG-U133 Plus 2.0 Array was applied to placental tissue from 4 RM cases (mean gestational age 63 days) and 6 elective abortions as controls (mean gestational age 62.8 days). Between the two groups 30 transcripts representing 27 genes showed differential expression. 10 genes with the highest fold-change were chosen for validation and further replicated in an independent sample set (9 RM cases, 17 controls) using Taqman® RT-qPCR. RM patients exhibited significant upregulation of two genes: apoptosis inducing ligand TRAIL (p=1.4x10-3) and S100A8 (p=7.9x10-4), encoding for inflammatory marker calprotectin. Combinatory effect of TRAIL, S100A8 and ASMTL provided a highly sensitive test distinguishing RM cases from controls (ROC analysis, area under curve=0.967). Immunohistochemical staining detected TRAIL and ASMTL mainly in trophoblastic cells and S100A8 in myeloid cells of maternal blood at maternal-fetal interface of first trimester placenta. In conclusion, genome wide expression profiling distinguished three differentially expressed genes in RM placentas: TRAIL, S100A8 and ASMTL. Although the detected gene expression alterations related to various pathways could be primary (causing) or secondary (consequence) events associated with the process of RM, the joint contribution of identified markers may provide a highly predictive test for detection of early pregnancy complications 10 gene arrays, 6 in control group and 4 in cases

ORGANISM(S): Homo sapiens

SUBMITTER: Sulev Koks 

PROVIDER: E-GEOD-22490 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress