title: Obesity-induced down-regulation of the mitochondrial translocator protein (TSPO) impairs placental steroid production.
abstract: BACKGROUND
  Low concentrations of estradiol and progesterone are hallmarks of adverse pregnancy outcomes as is maternal obesity. During pregnancy, placental cholesterol is the sole source of sex steroids. Cholesterol trafficking is the limiting step in sex steroid biosynthesis and is mainly mediated by the translocator protein (TSPO), present in the mitochondrial outer membrane.
  
  
  OBJECTIVE
  The objective of the study was to investigate the effects of maternal obesity in placental sex steroid biosynthesis and TSPO regulation.
  
  
  METHODS
  One hundred forty-four obese (body mass index 30-35 kg/m(2)) and 90 lean (body mass index 19-25 kg/m(2)) pregnant women (OP and LP, respectively) recruited at scheduled term cesarean delivery. Placenta and maternal blood were collected.
  
  
  METHODS
  This study was conducted at MetroHealth Medical Center (Cleveland, Ohio).
  
  
  METHODS
  Maternal metabolic components (fasting glucose, insulin, leptin, estradiol, progesterone, and total cholesterol) and placental weight were measured. Placenta (mitochondria and membranes separated) and cord blood cholesterol values were verified. The expression and regulation of TSPO and mitochondrial function were analyzed.
  
  
  RESULTS
  Plasma estradiol and progesterone concentrations were significantly lower (P < .04) in OP as compared with LP women. Maternal and cord plasma cholesterol were not different between groups. Placental citrate synthase activity and mitochondrial DNA, markers of mitochondrial density, were unchanged, but the mitochondrial cholesterol concentrations were 40% lower in the placenta of OP. TSPO gene and protein expressions were decreased 2-fold in the placenta of OP. In vitro trophoblast activation of the innate immune pathways with lipopolysaccharide and long-chain saturated fatty acids reduced TSPO expression by 2- to 3-fold (P < .05).
  
  
  CONCLUSIONS
  These data indicate that obesity in pregnancy impairs mitochondrial steroidogenic function through the negative regulation of mitochondrial TSPO.
authors.affiliation: Department of Reproductive Biology, Center for Reproductive Health, MetroHealth Medical Center, Cleveland, Ohio 44109-1998.
authors.forename: Luciana
authors.initials: L
authors.lastname: Lassance
authors.forename: Maricela
authors.initials: M
authors.lastname: Haghiac
authors.forename: Judi
authors.initials: J
authors.lastname: Minium
authors.forename: Patrick
authors.initials: P
authors.lastname: Catalano
authors.forename: Sylvie
authors.initials: S
authors.lastname: Hauguel-de Mouzon
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D015536:Down-Regulation / Q000502:physiology*; D004958:Estradiol / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007328:Insulin / Q000378:metabolism; D020738:Leptin / Q000378:metabolism; D009765:Obesity / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011374:Progesterone / Q000096:biosynthesis*; D018079:Receptors, GABA / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D007328:Insulin; D020738:Leptin; D018079:Receptors, GABA; C499229:TSPO protein, human; D011374:Progesterone; D004958:Estradiol; D002784:Cholesterol