title: Monocarboxylate transporter 8 expression in the human placenta: the effects of severe intrauterine growth restriction.
abstract: Thyroid hormones (THs) are essential for normal fetal development, with even mild perturbation in maternal thyroid status in early pregnancy being associated with neurodevelopmental delay in children. Transplacental transfer of maternal THs is critical, with increasing evidence suggesting a role for 3,3',5-tri-iodothyronine (T3) in development and function of the placenta itself, as well as in development of the central nervous and other organ systems. Intrauterine growth restriction (IUGR) is associated with fetal hypothyroxinaemia, a factor that may contribute to neurodevelopmental delay. The recent description of monocarboxylate transporter 8 (MCT8) as a powerful and specific TH membrane transporter, and the association of MCT8 mutations with profound neurodevelopmental delay, led us to explore MCT8 expression in placenta. We describe the expression of MCT8 in normal human placenta throughout gestation, and in normal third-trimester placenta compared with that associated with IUGR using quantitative reverse transcriptase PCR. MCT8 mRNA was detected in placenta from early first trimester, with a significant increase with advancing gestation (P=0.007). In the early third trimester, MCT8 mRNA was increased in IUGR placenta compared with normal samples matched for gestational age (P<0.05), but there was no difference between IUGR and normal placenta in the late third trimester. Western immunoblotting findings in IUGR and normal placentae were in accord with mRNA data. MCT8 immunostaining was demonstrated in villous cytotrophoblast and syncytiotrophoblast as well as extravillous trophoblast cells from the first trimester onwards with increasingly widespread immunoreactivity seen with advancing gestation. In conclusion, expression of MCT8 in placenta from early gestation is compatible with an important role in TH transport during fetal development and a specific role in placental development. Altered expression in placenta associated with IUGR may reflect a compensatory mechanism attempting to increase T3 uptake by trophoblast cells.
authors.affiliation: Department of Fetal Medicine, Division of Reproductive & Child Health, University of Birmingham, Edgbaston, Birmingham B15 2TG, UK.
authors.forename: S-Y
authors.initials: SY
authors.lastname: Chan
authors.forename: J A
authors.initials: JA
authors.lastname: Franklyn
authors.forename: H N
authors.initials: HN
authors.lastname: Pemberton
authors.forename: J N
authors.initials: JN
authors.lastname: Bulmer
authors.forename: T J
authors.initials: TJ
authors.lastname: Visser
authors.forename: C J
authors.initials: CJ
authors.lastname: McCabe
authors.forename: M D
authors.initials: MD
authors.lastname: Kilby
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D015153:Blotting, Western / Q000379:methods; D016022:Case-Control Studies; D005321:Extraembryonic Membranes / Q000737:chemistry / Q000378:metabolism; D005260:Female; D005317:Fetal Growth Retardation / Q000378:metabolism*; D005865:Gestational Age; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D027501:Monocarboxylic Acid Transporters / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D010920:Placenta / Q000737:chemistry / Q000378:metabolism*; D011247:Pregnancy; D011263:Pregnancy Trimester, Third; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D027981:Symporters; D013963:Thyroid Hormones / Q000378:metabolism; D014327:Trophoblasts / Q000737:chemistry / Q000378:metabolism
chemical_list: D027501:Monocarboxylic Acid Transporters; D012333:RNA, Messenger; C090735:SLC16A2 protein, human; D027981:Symporters; D013963:Thyroid Hormones