title: Labor inhibits placental mechanistic target of rapamycin complex 1 signaling.
abstract: BACKGROUND
  Labor induces a myriad of changes in placental gene expression. These changes may represent a physiological adaptation inhibiting placental cellular processes associated with a high demand for oxygen and energy (e.g., protein synthesis and active transport) thereby promoting oxygen and glucose transfer to the fetus. We hypothesized that mechanistic target of rapamycin complex 1 (mTORC1) signaling, a positive regulator of trophoblast protein synthesis and amino acid transport, is inhibited by labor.
  
  
  METHODS
  Placental tissue was collected from healthy, term pregnancies (n = 15 no-labor; n = 12 labor). Activation of Caspase-1, IRS1/Akt, STAT, mTOR, and inflammatory signaling pathways was determined by Western blot. NFĸB p65 and PPARγ DNA binding activity was measured in isolated nuclei.
  
  
  RESULTS
  Labor increased Caspase-1 activation and mTOR complex 2 signaling, as measured by phosphorylation of Akt (S473). However, mTORC1 signaling was inhibited in response to labor as evidenced by decreased phosphorylation of mTOR (S2448) and 4EBP1 (T37/46 and T70). Labor also decreased NFĸB and PPARγ DNA binding activity, while having no effect on IRS1 or STAT signaling pathway.
  
  
  CONCLUSIONS
  Several placental signaling pathways are affected by labor, which has implications for experimental design in studies of placental signaling. Inhibition of placental mTORC1 signaling in response to labor may serve to down-regulate protein synthesis and amino acid transport, processes that account for a large share of placental oxygen and glucose consumption. We speculate that this response preserves glucose and oxygen for transfer to the fetus during the stressful events of labor.
authors.affiliation: Center for Pregnancy and Newborn Research, Department of Obstetrics and Gynecology, University of Texas Health Science Center, San Antonio, TX 78229, USA. Electronic address: sml60@medschl.cam.ac.uk.
authors.forename: S
authors.initials: S
authors.lastname: Lager
authors.affiliation: Center for Pregnancy and Newborn Research, Department of Obstetrics and Gynecology, University of Texas Health Science Center, San Antonio, TX 78229, USA.
authors.forename: I L M H
authors.initials: IL
authors.lastname: Aye
authors.affiliation: Center for Pregnancy and Newborn Research, Department of Obstetrics and Gynecology, University of Texas Health Science Center, San Antonio, TX 78229, USA.
authors.forename: F
authors.initials: F
authors.lastname: Gaccioli
authors.affiliation: Center for Pregnancy and Newborn Research, Department of Obstetrics and Gynecology, University of Texas Health Science Center, San Antonio, TX 78229, USA.
authors.forename: V I
authors.initials: VI
authors.lastname: Ramirez
authors.affiliation: Center for Pregnancy and Newborn Research, Department of Obstetrics and Gynecology, University of Texas Health Science Center, San Antonio, TX 78229, USA.
authors.forename: T
authors.initials: T
authors.lastname: Jansson
authors.affiliation: Center for Pregnancy and Newborn Research, Department of Obstetrics and Gynecology, University of Texas Health Science Center, San Antonio, TX 78229, USA.
authors.forename: T L
authors.initials: TL
authors.lastname: Powell
mesh_terms: D000328:Adult; D020170:Caspase 1 / Q000378:metabolism; D005260:Female; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D007743:Labor, Obstetric / Q000378:metabolism*; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes / Q000378:metabolism*; D010766:Phosphorylation; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D014327:Trophoblasts / Q000378:metabolism; D055815:Young Adult
chemical_list: C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; D046912:Multiprotein Complexes; D000076222:Mechanistic Target of Rapamycin Complex 1; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D020170:Caspase 1
keywords: Insulin; MAPK; NFĸB; PPARγ; STAT; mTOR