Sema Avci1, Nilay Kuscu2, Begum Durkut2, Leyla Kilinc2, Ismail Ustunel2, Ciler Celik-Ozenci3,4. 1. Department of Histology and Embryology, School of Medicine, Alanya Alaaddin Keykubat University, Alanya, Turkey. 2. Department of Histology and Embryology, School of Medicine, Akdeniz University, Antalya, Turkey. 3. Department of Histology and Embryology, School of Medicine, Koc University, Istanbul, Turkey. cozenci@ku.edu.tr. 4. Koç University Research Center for Translational Medicine (KUTTAM), Koc University, Istanbul, Turkey. cozenci@ku.edu.tr.
Abstract
PURPOSE: This study aims to investigate whether indomethacin (IND) delays preterm birth by regulating the Notch pathway, Tlr receptors, and Sp-A in the placenta in lipopolysaccharide (LPS)-induced preterm labor (PTL) model. METHODS: CD-1 mice were distributed to the pregnant control (PC), Sham, PBS, IND (2 mg/kg; i.p.), LPS (25 μg/100 μl; intrauterine), and LPS + IND groups. The injections were performed on day 14.5 of pregnancy. Placentae were collected on day 15.5 of pregnancy, and immunohistochemical analyzes were performed. Differences in staining intensities between the Cox-1, Notch-1 (N1), Dll-1, Jagged-2 (Jag-2), Tlr-2, and Tlr-4 proteins were compared. RESULTS: Preterm labor rates were 100% and 66% (preterm delivery delayed 5 h) in the LPS and LPS + IND groups, respectively. In LPS-treated mice, a general morphological deterioration was observed in the placenta. Total placental mid-sagittal measurement was significantly reduced in the LPS-treated group, while it was similar to the PC group in the LPS + IND group. Cox-1 expression in the LZ increased, and Sp-A expression decreased after LPS injection, and IND administration diminished this increase. N1 expression increased in the labyrinth zone (LZ) and the junctional zone (JZ). Dll-1 and Jag-2 expression increased in the JZ after LPS injection (p < 0.0001). IND administration diminished Tlr-2 expression in the LZ and Tlr-4 expression in the JZ after LPS injection. CONCLUSION: In conclusion, PG (prostaglandin) inhibition may alter Notch signaling, Tlr, and Sp-A protein expression and may be associated with delayed labor in LPS-induced mice.
PURPOSE: This study aims to investigate whether indomethacin (IND) delays preterm birth by regulating the Notch pathway, Tlr receptors, and Sp-A in the placenta in lipopolysaccharide (LPS)-induced preterm labor (PTL) model. METHODS: CD-1 mice were distributed to the pregnant control (PC), Sham, PBS, IND (2 mg/kg; i.p.), LPS (25 μg/100 μl; intrauterine), and LPS + IND groups. The injections were performed on day 14.5 of pregnancy. Placentae were collected on day 15.5 of pregnancy, and immunohistochemical analyzes were performed. Differences in staining intensities between the Cox-1, Notch-1 (N1), Dll-1, Jagged-2 (Jag-2), Tlr-2, and Tlr-4 proteins were compared. RESULTS: Preterm labor rates were 100% and 66% (preterm delivery delayed 5 h) in the LPS and LPS + IND groups, respectively. In LPS-treated mice, a general morphological deterioration was observed in the placenta. Total placental mid-sagittal measurement was significantly reduced in the LPS-treated group, while it was similar to the PC group in the LPS + IND group. Cox-1 expression in the LZ increased, and Sp-A expression decreased after LPS injection, and IND administration diminished this increase. N1 expression increased in the labyrinth zone (LZ) and the junctional zone (JZ). Dll-1 and Jag-2 expression increased in the JZ after LPS injection (p < 0.0001). IND administration diminished Tlr-2 expression in the LZ and Tlr-4 expression in the JZ after LPS injection. CONCLUSION: In conclusion, PG (prostaglandin) inhibition may alter Notch signaling, Tlr, and Sp-A protein expression and may be associated with delayed labor in LPS-induced mice.
Authors: Victoria V Snegovskikh; Vineet Bhandari; Jo Rae Wright; Serkalem Tadesse; Thomas Morgan; Colin Macneill; Nastaran Foyouzi; Joong Shin Park; Yuguang Wang; Errol R Norwitz Journal: J Clin Endocrinol Metab Date: 2011-01-26 Impact factor: 5.958
Authors: Shrikant Bollapragada; Shrikant Bollopragada; Refaat Youssef; Fiona Jordan; Ian Greer; Jane Norman; Scott Nelson Journal: Am J Obstet Gynecol Date: 2009-01 Impact factor: 8.661
Authors: G A Gross; T Imamura; C Luedke; S K Vogt; L M Olson; D M Nelson; Y Sadovsky; L J Muglia Journal: Proc Natl Acad Sci U S A Date: 1998-09-29 Impact factor: 11.205