title: Expression of thyroid hormone transporters in the human placenta and changes associated with intrauterine growth restriction.
abstract: Thyroid hormones (TH) are important for the development of the human fetus and placenta from very early gestation. The transplacental passage of TH from mother to fetus and the supply of TH into trophoblasts require the expression of placental TH plasma membrane transporters. We describe the ontogeny of the TH transporters MCT8, MCT10, LAT1, LAT2, OATP1A2 and OATP4A1 in a large series (n = 110) of normal human placentae across gestation and describe their expression changes with intrauterine fetal growth restriction (IUGR n = 22). Quantitative RT-PCR revealed that all the mRNAs encoding TH transporters are expressed in human placenta from 6 weeks gestation and throughout pregnancy. MCT8, MCT10, OATP1A2 and LAT1 mRNA expression increased with gestation. OATP4A1 and CD98 (LATs obligatory associated protein) mRNA expression reached a nadir in mid-gestation before increasing towards term. LAT2 mRNA expression did not alter throughout gestation. Immunohistochemistry localised MCT10 and OATP1A2 to villous cytotrophoblasts and syncytiotrophoblasts, and extravillous trophoblasts while OATP4A1 was preferentially expressed in the villous syncytiotrophoblasts. Whilst MCT8 protein expression was increased, MCT10 mRNA expression was decreased in placentae from IUGR pregnancies delivered in the early 3rd trimester compared to age matched appropriately grown for gestational age controls. No significant change was found in the mRNA expression of the other transporters with IUGR. In conclusion, several TH transporters are present in the human placenta from early 1st trimester with varying patterns of expression throughout gestation. Their coordinated effects may regulate both transplacental TH passage and TH supply to trophoblasts, which are critical for the normal development of the fetus and placenta. Increased MCT8 and decreased MCT10 expression within placentae of pregnancies complicated by IUGR may contribute to aberrant development of the fetoplacental unit.
authors.affiliation: School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, UK.
authors.forename: L S
authors.initials: LS
authors.lastname: Loubière
authors.forename: E
authors.initials: E
authors.lastname: Vasilopoulou
authors.forename: J N
authors.initials: JN
authors.lastname: Bulmer
authors.forename: P M
authors.initials: PM
authors.lastname: Taylor
authors.forename: B
authors.initials: B
authors.lastname: Stieger
authors.forename: F
authors.initials: F
authors.lastname: Verrey
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: D026921:Amino Acid Transport Systems, Neutral / Q000096:biosynthesis*; D005260:Female; D005317:Fetal Growth Retardation / Q000378:metabolism*; D006801:Humans; D027283:Large Neutral Amino Acid-Transporter 1 / Q000096:biosynthesis; D027501:Monocarboxylic Acid Transporters / Q000096:biosynthesis*; D027361:Organic Anion Transporters / Q000096:biosynthesis; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D027981:Symporters; D013963:Thyroid Hormones / Q000378:metabolism*; D014327:Trophoblasts / Q000378:metabolism
chemical_list: D026921:Amino Acid Transport Systems, Neutral; D027283:Large Neutral Amino Acid-Transporter 1; D027501:Monocarboxylic Acid Transporters; D027361:Organic Anion Transporters; D012333:RNA, Messenger; C498964:SLC16A10 protein, human; C090735:SLC16A2 protein, human; C512988:SLCO1A2 protein, human; C498174:SLCO4A1 protein, human; D027981:Symporters; D013963:Thyroid Hormones