Nes are known to play a role in immune cell signaling. Lipid metabolism is also an important component of pregnancy and the timing of labor. Fatty acids of the n-3 and n-6 series can modify gestational length (Allen and Harris 2001; Wathes et al. 2007) through altered prostaglandin production (Elmes et al. 2004) and oxytocin signaling (Kim et al. 2012). Glutathione-s-transferase alpha 4 (Gsta4) is a DEG within this network closely linked to metabolism of n-6 polyunsaturated fatty acids. Gsta4 associates with membranes and mitochondria (Gardner and Gallagher 2001) to detoxify and remove the lipid peroxide end product 4hydroxynonenal (4HNE) from cells (Chapple et al. 2013). The network also included two genes associated with roles in ion channels and ion transporters: Solute Carrier Family 12 (sodium/potassium/chloride transporter) member 1 (Slc12a1) (decreased threefold with increasing maternal age) and solute carrier family 4, sodium borate transporter member 11 (Slc4a11) (upregulated 1.6-fold).qPCR analysisTo validate the array data, uterine samples were analyzed by qPCR for 18 DEG and one reference gene, cyclophilin.?2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.2015 | Vol. 3 | Iss. 4 | e12305 PageAging Effects on Uterine ContractilityM. Elmes et al.Table 5. Top 20 canonical subpathways from IPA analysis (all P < 0.001) associated with immune or inflammatory response and lipid transport and metabolism differentially expressed in laboring uterine horn with increasing maternal age. Subpathway Graft-versus-Host disease signaling LXR/RXR activation Granulocyte adhesion and diapedesis FXR/RXR activation Agranulocyte adhesion and diapedesis Autoimmune thyroid disease signaling Allograft rejection signaling Cytotoxic T-lymphocyte-mediated apoptosis of target cells Glucocorticoid receptor signaling Role of IL-17A in psoriasis Atherosclerosis signaling Oncostatin M signaling Inhibition of matrix metalloproteases Clathrin-mediated endocytosis signaling Altered T-cell and B-cell signaling in rheumatoid arthritis Bladder cancer signaling Granzyme B signaling Role of IL-17A in arthritis Type I diabetes mellitus signaling B cell development Gene symbol Prf1, HLA-C, Il1rn, HLA-B, HLA-DQB1, Gzmb Ttr, Apob, Apom, Apoh, Il1rn, Apoc2, Ptgs2 Cxcl3, Cxcl11, Mmp3, Il1rn, Cxcl14, Ccl21, mmp12, Cxcl6 Pparg, Apob, Il1rn, Foxa1, Apoc2, Mttp Cxcl3, Cxcl11, Mmp3, Il1rn, Cxcl14, Ccl21, mmp12, Cxcl6 Prf1, HLA-B, HLA-DQB1, Gzmb H2-T24, Prf1, HLA-B, HLA-DQB1, Gzmb H2-T24, Prf1, HLA-B, HLA-DQB1, Gzmb Cxcl3, Scgb1a1, Taf7 l, Il1rn, Plau, Ptgs2, Nppa, Cdkn1c, Cxcl3, Cxcl6 Apob, Apom, Mmp3, Il1rn, Apoc2 Mmp3, Plau, Chi3 l1, Adam12, Mmp3, mmp12, Apob, Apom,Ephb2, Figf, Apoc2, Fgf7 Il1rn, Ccl21,HLA-DQB1, Cd79a MMP Mmp33, Figf, mmp12, Fgf7, Prf1, Gzmb Cxcl3, Ptgs2, Cxcl6, Prf1,HLA-B,HLA-DQB1, Gzmb HLA-DQB1, Cd79aGenes in bold typeface were increased in laboring uterine horn from 6 month (OLDER) rat dams compared with YOUNG animals. Other genes were decreased.The selected list included the top nine genes that were identified as being either upregulated or downregulated in the array analysis. Expression of the reference gene was not altered by maternal age (P = 0.95). All the 18 genes tested by SART.S23503 qPCR showed similar changes in direction to those found by the array analysis (Table 7). In half of these the fold change was also significant (P < 0.05) whereas in the remaind.