SIRT1 Is a Novel Regulator of Key Pathways of Human Labor

Human swim (SIRT) 1 and SIRT2, which possess nicotin amide adenosine dinucleotide (NAD(+))-dependent deacetylase activity, exhibit anti-inflammatory actions However, there are no data available on SIRT1 and SIRT2 expression and regulation in human intrauterine tissues Thus, the aim of this study was to characterize the localization and expression of SIRT1 and SIRT2 in 1) placenta and fetal membranes before and after term spontaneous labor onset, 2) prelabor fetal membranes from the supracervical site (SCS) and a distal site (DS), and 3) in response to proinflammatory stimuli Further, the effect of SIRT activation using resveratrol and SRT1720 on prolabor mediators was also assessed SIRT1 and SIRT2 were localized in the syncytiotro phoblast layer and the cytotrophoblasts of the placenta, amnion epithelium, trophoblast layer of the chorion, and decidual cells Additionally, SIRT2 was found within the endothelial walls of placental vessels SIRT2, but not SIRT1, staining was significantly lower in amnion and chorion obtained from the SCS compared to a DS On the other hand, SIRT1, but not SIRT2, gene and/or protein expression was significantly lower in placenta, amnion, and chorion obtained after labor compared to prelabor SIRT1 expression, but not SIRT2, was down regulated by lipopolysac charide (LPS) and proinflammatory cytokines TNF and IL1B The SIRT1 activators resveratrol and SRT1720 significantly de creased LPS induced TNF, IL6, and IL8 gale expression and release and PTGS2 mRNA expression and resultant prostaglan din (PG) E-2 and PGF(2 alpha), release from human gestational tissues In conclusion, SIRT1 possesses anti-inflammatory actions and thus may play a role in regulating pregnancy and parturition