Microarray profiling of secretory-phase endometrium from patients with recurrent miscarriage

• Published in: Reproductive biology Vol. 12; no. 2; pp. 183 - 199
• Main Authors: Othman, Rosfayati, Omar, Mohd Hashim, Shan, Lim Pei, Shafiee, Mohd Nasir, Jamal, Rahman, Mokhtar, Norfilza Mohd
• Format: Journal Article
• Language: English
• Published: Poland Elsevier Urban & Partner Sp. z o.o 01.07.2012
• Subjects: Abortion, Habitual - metabolism; Computational Biology; Endometrium - metabolism; Female; gene expression; Gene Expression Regulation - genetics; Gene Expression Regulation - physiology; genomics; Humans; Integrin beta3 - metabolism; Luteal Phase - genetics; Luteal Phase - metabolism; Macrophage Colony-Stimulating Factor - metabolism; Malaysia; Matrix Metalloproteinases, Secreted - metabolism; microarray; Obstetrics and Gynecology; Pregnancy; Principal Component Analysis; Protein Array Analysis; Real-Time Polymerase Chain Reaction; recurrent miscarriage; Signal Transduction - genetics; Malaysia; recurrent miscarriage; genomics; microarray; gene expression
• ISSN: 1642-431X; 2300-732X
• DOI: 10.1016/S1642-431X(12)60085-0

The aim of the present study was to identify differentially expressed genes and their related biological pathways in the secretory phase endometrium from patients with recurrent miscarriage (RM) and fertile subjects. Endometrial samples from RM and fertile patients were analyzed using the Affymetrix GeneChip® ST Array. The bioinformatic analysis using the Partek Genomic Suite revealed 346 genes that were differentially expressed (175 up-regulated and 171 down-regulated) in the endometrium of RM patients compared to the fertile subjects (fold change ≥1.5, p<0.005). Validation step using quantitative real-time polymerase chain reaction (qPCR) confirmed a similar expression pattern of four exemplary genes: one up-regulated gene (fibroblast growth factor 9, FGF9) and three down-regulated genes: integrin β3 (ITGB3), colony stimulating factor 1 (CSF1) and matrix-metalloproteinases 19 (MMP19). The Gene Set Enrichment Analysis (GSEA) and the Pathway Studio Software have found 101 signaling pathways (p<0.05) associated with the affected genes including the FGFR3/signal transducer and activator of transcription (STAT) pathway and the CSF1R/STAT pathway. Cell adhesion, cell differentiation and angiogenesis were among biological processes indicated by this system. In conclusion, microarray technique is a useful tool to study gene expression in the secretory phase-endometrium of RM patients. The differences in endometrial gene expressions between healthy and RM subjects contribute to an increase in our knowledge on molecular mechanisms of RM development and may improve the outcome of pregnancies in high-risk women with RM.