Endocrine Abstracts

Thyroid hormones (TH) are important for the development of the fetus and placenta. We have previously reported increased placental expression of the potent TH transporter, MCT8, with advancing gestation. The amino acid plasma membrane transporters, MCT10, LAT1, LAT2, and the organic anion transporters, OATP1A2 and OATP4A1, are also known to transport TH.

Objective: To describe the ontogeny of these TH transporters and the obligate heterodimer of the LATs, 4F2hc, in human placenta and to assess changes in their expression with IUGR.

Methods: Placenta was collected from normal pregnancies ending at 6–20 weeks gestation (weeks) (n=61) and at caesarean sections of appropriately grown for gestational age (AGA; 27–41 weeks, n=57) or severe IUGR pregnancies (25–38 weeks, n=22) with ethical approval. Taqman RT-PCR was used to quantify relative mRNA expression.

Results: Placental MCT10 and LAT1 expressions increased with gestation (P<0.001) being reduced by 90 and 75% respectively at 6–20 weeks compared to term. 4F2hc, OATP1A2 and OATP4A1 expressions reached nadirs at 13–20 weeks being 75, 88 and 92% less respectively compared to term (P<0.05). LAT2 expression did not alter throughout gestation. IUGR placenta expressed 80% less (P<0.05) MCT10 than age-matched AGA placenta. No significant change was found in the placental expression of the other transporters with IUGR.

Conclusions: A range of TH transporters are present in the human placenta from the first trimester. Their coordinated effects may regulate transplacental TH passage and the development of the placenta itself through the progress of gestation. MCT10 and LAT1 may have more prominent roles in late gestation. At 13–20 weeks, lower expressions of 4F2hc, OATP1A2 and OATP4A1 coinciding with the onset of endogenous fetal TH production may be important in protecting the fetus from excessive TH exposure. In IUGR, decreased MCT10 expression may contribute to the lower circulating TH levels seen in IUGR fetuses and to malplacentation.