Table 2. Top canonical pathways and protein domains enriched among the 445 genes associated with intrauterine inflammation markers.
| IPA Canonical Pathways | p-value | Associated Genes | PFAM Protein Domains | p-value | Associated Genes | |
|---|---|---|---|---|---|---|
| Genes with Increased Expression Levels | Granulocyte Adhesion and Diapedesis | 1.58e-23 | IL1RL1, ITGAM, MMP9, SELL, CSF3R, CCL20, IL1R2, ITGB2, SELE, FPR1, VCAM1, CXCL6, CXCR4, IL1RN, IL1R1, C5AR1, CXCL1, CXCL5, CCL5, IL1B, TNFRSF1B, CXCL2, PPBP, CXCL8, TNFRSF11B, CCL2, SELPLG, MMP10, CXCL3, CSF3, ICAM1 | Small cytokines (intecrine/ chemokine), interleukin-8 like | 1.13e-4 | CCL2, CCL20, CCL5, CXCL1, CXCL2, CXCL5, IL8 |
| Hepatic Fibrosis / Hepatic Stellate Cell Activation | 1.58e-16 | IL1RL1, MMP9, IL1R2, IL6, VCAM1, IL10RA, IFNGR1, IL1R1, FLT1, IGFBP3, CCL5, IL1B, VEGFA, PDGFRA, CD14, TNFRSF1B, CXCL8, NFKB2, TNFRSF11B, COL11A1, CCL2, CXCL3, TIMP1, SERPINE1, ICAM1 | Metallothionein | 4.27e-2 | MT1H, MT1X, MT2A | |
| Atherosclerosis Signaling | 7.94e-16 | CCR2, S100A8, IL1B, MMP9, ITGB2, SELE, IL6, VCAM1, CXCL8, ALOX5, NFKB2, LYZ, CXCR4, IL1RN, CCL2, SELPLG, SERPINA1, F3, PLBD1, ICAM1, PLA2G2A | S-100/ ICaBP type calcium binding domain | 4.27e-2 | S100A4, S100A8, S100A9, S100P | |
| Genes with Decreased Expression Levels | Gap Junction Signaling | 2.04e-5 | CAV1, GUCY1A2, GUCY1A3, GAB1, PLCE1, PRKAG2, PLCL1 | Immunoglobulin I-set domain | 1.83e-3 | CNTN1, NEGR1, NTRK3, OPCML, ROR1 |
| Cellular Effects of Sildenafil (Viagra) | 4.57e-5 | MYH3, GUCY1A2, PLCE1, GUCY1A3, PRKAG2, PLCL1 | ||||
| Dopamine-DARPP32 Feedback in cAMP Signaling | 1.55e-4 | GUCY1A2, GUCY1A3, PPM1L, PLCE1, PRKAG2, PLCL1 |
The top three most significant pathways (right-tailed Fisher’s Exact test p-value < 0.0001) and significant protein domains (FDR p-value < 0.05) are listed. Network analyses were stratified by gene expression directionality. Genes that displayed increased expression levels in association with one or histological markers of intrauterine inflammation were enriched for canonical pathways and protein domains involved in inflammatory and immune processes. Genes that displayed decreased expression levels in association with one or histological markers of intrauterine inflammation were enriched for canonical pathways and protein domains involved early neuronal development.