Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2010) 21 P315

SFEBES2009 Poster Presentations Reproduction (23 abstracts)

The role of thyroid hormone transporters MCT8 and MCT10 in the EVT-like cell line HTR8-SVneo

Juhela Choudhury , Laurence Loubiere , Elisavet Vasilopoulou , Christopher McCabe , Jayne Franklyn , Mark Kilby & Shiao Chan


University of Birmingham, Birmingham, West Midland, UK.


Thyroid hormones (THs) are important for fetal and placental development. Monocarboxylate transporters 8 and 10 (MCT8 and MCT10) are effective plasma membrane TH transporters expressed in the human placenta from 6 weeks of gestation. Both have been localized to human villous trophoblasts and extravillous trophoblasts (EVTs).

Aims: Using HTR-8/SVneo cells as a model of 1st trimester EVTs, we assessed 1) T3 effects on gene expression, cell proliferation and invasion and 2) the effect of altered MCT8 or MCT10 expression on proliferation and apoptosis; and whether effects were T3-mediated.

Methods: 1) Cells were cultured in presence of 0–100 nM T3 and cell proliferation was assessed (MTT assay) at 24–96 h. Cells were treated with T3 (0 vs 10 nM) to assess gene expression (quantitative RT-PCR, 2–48 h) and cell invasion into Matrigel (48 h). 2) MCT8 was down-regulated; MCT8 and MCT10 were over-expressed (siRNA, plasmid Nucleofection); followed by 48 h treatment with T3 (0 vs 10 nM). Effects on proliferation (MTT assay) and apoptosis (caspase3/7 activity) were assessed.

Results: T3 treatment did not affect HTR-8/SVneo proliferation (n=3) nor alter the mRNA expressions (n=5) of TH responsive genes TH receptor β1 and Connexin43, the pre-receptor regulators of T3 action, deiodinases 2 and 3, nor their own transporters, MCT8 and MCT10. However, T3 treatment increased the number of invading cells by threefold (n=1).

Over-expression of MCT8 or MCT10 reduced cell proliferation by 36 and 29% respectively (n=4, P<0.05) in the presence of T3. Apoptosis was reduced, independently of T3 treatment, by 29% (n=4) and 16% (n=3) respectively (P<0.005). Conversely, down-regulation of MCT8 resulted in increased apoptosis independently of T3 (n=3, P<0.003).

Conclusions: Like primary EVTs, HTR-8/SVneo cells become more invasive with T3 treatment. MCT8 and MCT10 may have both T3-dependent (suppress proliferation) and T3-independent (reduce apoptosis) effects in EVTs. This suggests an important role for MCT8 and MCT10 in human placental development.

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