Endocrine Abstracts

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.