title: The long non-coding RNA NEAT1 is increased in IUGR placentas, leading to potential new hypotheses of IUGR origin/development.
abstract: BACKGROUND
  Intrauterine Growth Restriction (IUGR) is a multifactorial disease defined by an inability of the fetus to reach its growth potential. IUGR not only increases the risk of neonatal mortality/morbidity, but also the risk of metabolic syndrome during adulthood. Certain placental proteins have been shown to be implicated in IUGR development, such as proteins from the GH/IGF axis and angiogenesis/apoptosis processes.
  
  
  METHODS
  Twelve patients with term IUGR pregnancy (birth weight < 10th percentile) and 12 CTRLs were included. mRNA was extracted from the fetal part of the placenta and submitted to a subtraction method (Clontech PCR-Select cDNA Subtraction).
  
  
  RESULTS
  One candidate gene identified was the long non-coding RNA NEAT1 (nuclear paraspeckle assembly transcript 1). NEAT1 is the core component of a subnuclear structure called paraspeckle. This structure is responsible for the retention of hyperedited mRNAs in the nucleus. Overall, NEAT1 mRNA expression was 4.14 (±1.16)-fold increased in IUGR vs. CTRL placentas (P = 0.009). NEAT1 was exclusively localized in the nuclei of the villous trophoblasts and was expressed in more nuclei and with greater intensity in IUGR placentas than in CTRLs. PSPC1, one of the three main proteins of the paraspeckle, co-localized with NEAT1 in the villous trophoblasts. The expression of NEAT1_2 mRNA, the long isoform of NEAT1, was only modestly increased in IUGR vs. CTRL placentas.
  
  
  CONCLUSIONS
  The increase in NEAT1 and its co-localization with PSPC1 suggests an increase in paraspeckles in IUGR villous trophoblasts. This could lead to an increased retention of important mRNAs in villous trophoblasts nuclei. Given that the villous trophoblasts are crucial for the barrier function of the placenta, this could in part explain placental dysfunction in idiopathic IUGR fetuses.
authors.affiliation: Clinic of Neonatology, University Hospital and University of Lausanne, Switzerland. Electronic address: sandrine.gremlich-irrausch@chuv.ch.
authors.forename: S
authors.initials: S
authors.lastname: Gremlich
authors.affiliation: Department of Gynecology, Obstetrics and Medical Genetics, University Hospital and University of Lausanne, Switzerland.
authors.forename: F
authors.initials: F
authors.lastname: Damnon
authors.affiliation: Department of Gynecology, Obstetrics and Medical Genetics, University Hospital and University of Lausanne, Switzerland.
authors.forename: D
authors.initials: D
authors.lastname: Reymondin
authors.affiliation: Service of Biomedicine, University Hospital and University of Lausanne, Switzerland.
authors.forename: O
authors.initials: O
authors.lastname: Braissant
authors.affiliation: Institute of Anatomy, University of Bern, Switzerland.
authors.forename: J C
authors.initials: JC
authors.lastname: Schittny
authors.affiliation: Department of Gynecology, Obstetrics and Medical Genetics, University Hospital and University of Lausanne, Switzerland.
authors.forename: D
authors.initials: D
authors.lastname: Baud
authors.affiliation: Department of Gynecology, Obstetrics and Medical Genetics, University Hospital and University of Lausanne, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Gerber
authors.affiliation: Clinic of Neonatology, University Hospital and University of Lausanne, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Roth-Kleiner
mesh_terms: D000328:Adult; D002467:Cell Nucleus / Q000378:metabolism; D005260:Female; D005317:Fetal Growth Retardation / Q000503:physiopathology*; D006801:Humans; D010920:Placenta / Q000503:physiopathology*; D011247:Pregnancy; D062085:RNA, Long Noncoding / Q000378:metabolism*; D014327:Trophoblasts / Q000378:metabolism*
chemical_list: C577276:NEAT1 long non-coding RNA, human; D062085:RNA, Long Noncoding
keywords: IUGR; Non-coding RNA; Trophoblast