title: Maternal obesity is associated with a reduction in placental taurine transporter activity.
abstract: OBJECTIVE
  Maternal obesity increases the risk of poor pregnancy outcome including stillbirth, pre-eclampsia, fetal growth restriction and fetal overgrowth. These pregnancy complications are associated with dysfunctional syncytiotrophoblast, the transporting epithelium of the human placenta. Taurine, a β-amino acid with antioxidant and cytoprotective properties, has a role in syncytiotrophoblast development and function and is required for fetal growth and organ development. Taurine is conditionally essential in pregnancy and fetal tissues depend on uptake of taurine from maternal blood. We tested the hypothesis that taurine uptake into placental syncytiotrophoblast by the taurine transporter protein (TauT) is lower in obese women (body mass index (BMI)⩾30 kg m(-)(2)) than in women of ideal weight (BMI 18.5-24.9 kg m(-)(2)) and explored potential regulatory factors.
  
  
  METHODS
  Placentas were collected from term (37-42-week gestation), uncomplicated, singleton pregnancies from women with BMI 19-49 kg m(-)(2). TauT activity was measured as the Na(+)-dependent uptake of (3)H-taurine into placental villous fragments. TauT expression in membrane-enriched placental samples was investigated by western blot. In vitro studies using placental villous explants examined whether leptin or IL-6, adipokines/cytokines that are elevated in maternal obesity, regulates TauT activity.
  
  
  RESULTS
  Placental TauT activity was significantly lower in obese women (BMI⩾30) than women of ideal weight (P<0.03) and inversely related to maternal BMI (19-49 kg m(-)(2); P<0.05; n=61). There was no difference in TauT expression between placentas of ideal weight and obese class III (BMI⩾40) subjects. Long-term exposure (48 h) of placental villous explants to leptin or IL-6 did not affect TauT activity.
  
  
  CONCLUSIONS
  Placental TauT activity at term is negatively related to maternal BMI. We propose that the reduction in placental TauT activity in maternal obesity could lower syncytiotrophoblast taurine concentration, compromise placental development and function, and reduce the driving force for taurine efflux to the fetus, thereby increasing the risk of poor pregnancy outcome.
authors.affiliation: 1] Maternal and Fetal Health Research Centre, Institute of Human Development, University of Manchester, Manchester, UK [2] Maternal and Fetal Health Research Centre, St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
authors.forename: A M
authors.initials: AM
authors.lastname: Ditchfield
authors.affiliation: 1] Maternal and Fetal Health Research Centre, Institute of Human Development, University of Manchester, Manchester, UK [2] Maternal and Fetal Health Research Centre, St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
authors.forename: M
authors.initials: M
authors.lastname: Desforges
authors.affiliation: 1] Maternal and Fetal Health Research Centre, Institute of Human Development, University of Manchester, Manchester, UK [2] Maternal and Fetal Health Research Centre, St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
authors.forename: T A
authors.initials: TA
authors.lastname: Mills
authors.affiliation: 1] Maternal and Fetal Health Research Centre, Institute of Human Development, University of Manchester, Manchester, UK [2] Maternal and Fetal Health Research Centre, St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
authors.forename: J D
authors.initials: JD
authors.lastname: Glazier
authors.affiliation: 1] Maternal and Fetal Health Research Centre, Institute of Human Development, University of Manchester, Manchester, UK [2] Maternal and Fetal Health Research Centre, St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
authors.forename: M
authors.initials: M
authors.lastname: Wareing
authors.affiliation: 1] Maternal and Fetal Health Research Centre, Institute of Human Development, University of Manchester, Manchester, UK [2] Maternal and Fetal Health Research Centre, St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
authors.forename: K
authors.initials: K
authors.lastname: Mynett
authors.affiliation: 1] Maternal and Fetal Health Research Centre, Institute of Human Development, University of Manchester, Manchester, UK [2] Maternal and Fetal Health Research Centre, St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
authors.forename: C P
authors.initials: CP
authors.lastname: Sibley
authors.affiliation: 1] Maternal and Fetal Health Research Centre, Institute of Human Development, University of Manchester, Manchester, UK [2] Maternal and Fetal Health Research Centre, St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
authors.forename: S L
authors.initials: SL
authors.lastname: Greenwood
mesh_terms: D000328:Adult; D015153:Blotting, Western; D015992:Body Mass Index; D002352:Carrier Proteins / Q000096:biosynthesis / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D002824:Chorionic Villi / Q000378:metabolism; D005260:Female; D005317:Fetal Growth Retardation / Q000209:etiology / Q000378:metabolism*; D006801:Humans; D007231:Infant, Newborn; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D009765:Obesity / Q000150:complications / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism* / Q000503:physiopathology; D011225:Pre-Eclampsia / Q000209:etiology / Q000378:metabolism*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000378:metabolism*; D050497:Stillbirth; D013654:Taurine / Q000378:metabolism*; D000099247:Taurine Transporters
chemical_list: D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D013654:Taurine; D000099247:Taurine Transporters