1. Transcriptional profiling with a pathway-oriented analysis in the placental villi of unexplained miscarriage
- Author
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Sung Han Shim, Dong Hyun Cha, Se Ra Sung, Tae Ki Yoon, Haengseok Song, You Shin Kim, Woo Sik Lee, J.A. Yoon, Mi-Uk Chin, and Sang Woo Lyu
- Subjects
Adult ,Genome-wide association study ,medicine.disease_cause ,Oxidative Phosphorylation ,Miscarriage ,Andrology ,Pregnancy ,medicine ,Humans ,Gene Regulatory Networks ,KEGG ,biology ,Superoxide Dismutase ,Gene Expression Profiling ,Case-control study ,Obstetrics and Gynecology ,medicine.disease ,Glutathione ,Mitochondria ,Abortion, Spontaneous ,Gene expression profiling ,Oxidative Stress ,Glutathione S-transferase ,Reproductive Medicine ,Case-Control Studies ,Immunology ,biology.protein ,Female ,Chorionic Villi ,Reactive Oxygen Species ,Oxidative stress ,Genome-Wide Association Study ,Signal Transduction ,Developmental Biology - Abstract
Introduction Miscarriage is the most common placental-related complication of pregnancy. It has been extensively investigated to discover the underlying mechanism(s) by which miscarriage occurs, but in many cases the etiology still remains unclear. The aim of this study was to analyze genome-wide expression profiles of placental villi (PV) from unexplained miscarriage with a pathway-oriented method for identifying underlying mechanism(s) of unexplained miscarriage. Methods We investigated PV of 18 women with unexplained miscarriage and 11 women underwent normal pregnancy. Each PV was obtained through dilatation & evacuation and chorionic villous sampling, respectively. Genome-wide expression profiles of PV were analyzed by Gene Set Enrichment Analysis (GSEA) to find dysregulated signaling pathways in PV of unexplained miscarriage. Results Unsupervised hierarchical clustering showed heterogeneity of expression profiles between PV of normal developing pregnancy and unexplained miscarriage. GSEA, a supervised analysis, with KEGG pathways revealed that several gene sets associated with mitochondrial function including glutathione metabolism and oxidative phosphorylation are dysregulated in PV from unexplained miscarriage. RT-PCR, real-time RT-PCR and/or immunohistochemistry reinforced that expression of genes constituting these gene sets enriched in normal pregnancy and Cu/Zn-superoxide dismutase was down-regulated in PV of unexplained miscarriage. Discussion Structural vulnerability of placental villi for reactive oxygen species (ROS), which is caused by systemic down-regulation of mitochondrial pathways involved in mitochondrial redox balance and functions, aggravates oxidative stress with increased ROS production in PV of unexplained miscarriage. Conclusion Systemic vulnerability for ROS in PV could be a major cause of unexplained miscarriage.
- Published
- 2013
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