title: Differential triiodothyronine responsiveness and transport by human cytotrophoblasts from normal and growth-restricted pregnancies.
abstract: BACKGROUND
  Abnormal placentation in human pregnancy is associated with intrauterine fetal growth restriction (IUGR). Our group has previously reported the association between severe IUGR, lower fetal circulating concentrations of thyroid hormones (THs), and altered expression of TH receptors and TH transporters within human placental villi. We postulate that altered TH bioavailability to trophoblasts may contribute to the pathogenesis of IUGR.
  
  
  OBJECTIVE
  Cytotrophoblasts were isolated from normal and IUGR human placentae to compare their responsiveness to T(3) and their capability for T(3) transport.
  
  
  RESULTS
  Compared with normal cytotrophoblasts, the viability of IUGR cytotrophoblasts (assessed by methyltetrazoleum assay) was significantly reduced (P < 0.001), whereas apoptosis (assessed using caspase 3/7 activity and M30 immunoreactivity) was significantly increased after T(3) treatment for 48 h (P < 0.001 and P < 0.01, respectively). The secretion of human chorionic gonadotropin was significantly increased by IUGR cytotrophoblasts compared with normal cytotrophoblasts (P < 0.001), independently of T(3) treatment. Net transport of [(125)I]T(3) was 20% higher by IUGR cytotrophoblasts compared with normal cytotrophoblasts (P < 0.001), and this was accompanied by a 2-fold increase in the protein expression of the TH transporter, monocarboxylate transporter 8, as assessed by Western immunoblotting (P < 0.01).
  
  
  CONCLUSIONS
  IUGR cytotrophoblasts demonstrate altered responsiveness to T(3) with significant effects on cell survival and apoptosis compared with normal cytotrophoblasts. Increased monocarboxylate transporter 8 expression and intracellular T(3) accumulation may contribute to the altered T(3) responsiveness of IUGR cytotrophoblasts.
authors.affiliation: School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, United Kingdom.
authors.forename: E
authors.initials: E
authors.lastname: Vasilopoulou
authors.forename: L S
authors.initials: LS
authors.lastname: Loubière
authors.forename: A
authors.initials: A
authors.lastname: Martín-Santos
authors.forename: C J
authors.initials: CJ
authors.lastname: McCabe
authors.forename: J A
authors.initials: JA
authors.lastname: Franklyn
authors.forename: M D
authors.initials: MD
authors.lastname: Kilby
authors.forename: S-Y
authors.initials: SY
authors.lastname: Chan
mesh_terms: D000328:Adult; D026921:Amino Acid Transport Systems, Neutral / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001692:Biological Transport / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000378:metabolism; D005260:Female; D005317:Fetal Growth Retardation / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008297:Male; D027501:Monocarboxylic Acid Transporters / Q000235:genetics / Q000378:metabolism; D010920:Placenta / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D027981:Symporters; D014284:Triiodothyronine / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology*; D014327:Trophoblasts / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D055815:Young Adult
chemical_list: D026921:Amino Acid Transport Systems, Neutral; D006063:Chorionic Gonadotropin; D027501:Monocarboxylic Acid Transporters; C498964:SLC16A10 protein, human; C090735:SLC16A2 protein, human; D027981:Symporters; D014284:Triiodothyronine