Fetal membranes as an interface between inflammation and metabolism: Increased Aquaporin 9 expression in the presence of spontaneous labor at term and chorioamnionitis

Abstract

Objective. Aquaporin 9 (AQP9) is a water channel protein characterized by its high permeability to nutrients such as lactate and glycerol, as well as urea and other small solutes. These unique properties of AQP9 suggest that this molecule may play a role in the modulation of nutrient flux through the fetal membranes in conditions associated with increased metabolic demand, such as spontaneous labor and inflammation. The objective of this study was to determine the expression of AQP9 in the chorioamniotic membranes from women with and without term labor, as well as those with preterm prelabor rupture of membranes (PPROM) with and without histologic chorioamnionitis. Study design. A cross-sectional study was performed which included patients in the following groups: (1) term not in labor (TNL; n ¼ 14); (2) term, spontaneous labor (n ¼ 14); and (3) PPROM with (n ¼ 20) and without (n ¼ 17) histologic chorioamnionitis. AQP9 mRNA expression in fetal membranes was quantified using quantitative real-time reverse transcription-polymerase chain reaction and analyzed with a linear model including gestational age as a covariate. Results. (1) AQP9 mRNA expression was identified in all chorioamniotic membrane specimens; (2) AQP9 expression in fetal membranes was significantly higher in spontaneous term labor when compared with TNL (fold change 3.6; p ¼ 0.01); and (3) Among patients with PPROM, the presence of histologic chorioamnionitis was associated with a higher expression of AQP9 in the chorioamniotic membranes compared with those from women without histologic chorioamnionitis (fold change 8.7; p 5 0.001). Conclusion. Aquaporin 9 mRNA expression is higher in the fetal membranes from patients with spontaneous term labor and those with PPROM and histologic chorioamnionitis. These findings are novel, and suggest a role for aquaporin 9 in membrane-mediated transfer of nutrients to support the increased metabolic demands associated with the host immune response of the terminal pathway of parturition and histologic chorioamnionitis.

Cellular and subcellular localization of aquaporins 1, 3, 8, and 9 in amniotic membranes during pregnancy in mice

“…Increases in TNF-α expression in amniotic fluid and apoptotic cells in the amniotic membranes are observed in patients undergoing spontaneous delivery with labor and in patients with chorioamnionitis (Hayashi et al 2008;Kataoka et al 2002;Lei et al 1996;Maymon et al 1999). AQP9 expression increases in the presence of spontaneous labor at term and chorioamnionitis (Mittal et al 2009). Thus, AQP9 is closely related to apoptosis and TNF-α.…”

Characterization of the myometrial transcriptome and biological pathways of spontaneous human labor at term

“…Each of these pathways is central in the deployment of an inflammatory response: cytokine-cytokine receptor interaction, Jak-STAT signaling, the complement and coagulation pathway, NOD-like receptor signaling, systemic lupus erythematosus (specifically the complement C1q complex), and chemokine signaling. Interestingly, components of these pathways have been previously linked to both normal parturition [57, 75, 76, 159, 180, 201, 213, 221, 226–228, 235, 271, 274, 308] and the “Great Obstetrical Syndromes” [32, 33, 64, 79–82, 84, 85, 89, 238, 267, 291, 295, 307, 320], including preterm labor [28, 58, 74, 77, 83, 86–88, 119, 120, 164, 165, 211, 223, 246, 252, 254, 290, 292, 293, 316–319]. Indeed, our group has reported an association between activation of the NALP3 inflammasome and the common pathway of parturition [119].…”

Assisted Reproduction and Preterm Birth

“…Women with preterm labor who delivered preterm had a higher median thrombin anti-thrombin III concentration than those who delivered at term (Erez, Romer et al, 2009). This was particularly evident among those without intra-amniotic infection/inflammation, in which elevated amniotic fluid of thrombin anti-thrombin complex concentrations were associated with a shorter amniocentesis to delivery interval and a lower gestational age at delivery than those with normal or low concentrations of this complex (Erez,Romero,et al,2009). A vanishing twin can be an additional possible source for increase intrauterine thrombin generation that may lead to preterm birth.…”

“…. Evidence in support of the increase activation of the coagulation cascade among patients with preterm labor and intact membranes as well as women with preterm PROM include: 1) women with spontaneous preterm labor without intra-amniotic infection or inflammation and women with vaginal bleeding who delivered preterm, have a lower median maternal plasma protein Z (a co factor of protein Z dependent protease inhibitor that inhibits the activity of factor X) than that of normal pregnant women ; 2) regardless to the presence of intra-amniotic infection/inflammation, women with preterm labor and intact membranes have a higher median tissue factor activity and a lower median tissue factor pathway inhibitor than those with a normal pregnancy 3) patients with preterm PROM have a higher median maternal plasma tissue factor concentration and a lower median TFPI concentrations than normal pregnant women Moreover, increased thrombin generation was detected not only in the maternal circulation but also in the amniotic fluid (Erez,Romero,et al,2009). Women with preterm labor who delivered preterm had a higher median thrombin anti-thrombin III concentration than those who delivered at term (Erez, Romer et al, 2009).…”