Thyroid hormones (TH) are important for the development of the fetus and placenta. Monocarboxylate transporter 8 (MCT8) is a potent plasma membrane TH transporter, present in the human placenta from 6 weeks of gestation. Its expression increases significantly with advancing gestational age. We postulate that MCT8 plays an important role in human placental development.
Objective: To assess the effects of altered MCT8 expression on the survival, syncytialisation and invasion of trophoblasts from human term placentae.
Methods: Cytotrophoblasts (CTs) were isolated from normal term placentae (n=5) and MCT8 expression was downregulated (using siRNA) and upregulated (plasmid transfection) followed by 48 h treatment with T3 (10 nM). CT viability (MTT assay), apoptosis (Caspase 3/7 activity) and syncytialisation (total HCG secretion) were assessed. Using SGHPL-4 cells as a model of first trimester extravillous trophoblast (EVT) the effect of MCT8 on cell invasion into Matrigel after 4872 h treatment with T3 (10 nM) was investigated.
Results: Overexpression of MCT8 decreased CT viability by 20% both in the presence (P<0.001) and absence (P<0.01) of T3, while downregulation of MCT8 expression resulted in increased CT viability by 20% (P<0.01 at 0 nM T3). Downregulation and overexpression of MCT8 in CTs did not cause a significant change in Caspase 3/7 activity nor HCG secretion. In the presence of T3 overexpression of MCT8 in SGHPL-4 cells increased the number of cells that invaded by 2.5-fold compared to vector only control (P<0.05).
Conclusions: MCT8 adversely affects the viability of human term CTs both in the presence and absence of T3, an effect that is not mediated through the apoptotic pathway. MCT8 is not implicated in CT syncytialisation. Overexpression of MCT8 amplifies the pro-invasive effect of T3 on SGHPL-4 cells. These results indicate that MCT8 affects trophoblast cells via both T3-dependent and T3-independent mechanisms and suggest an important role for MCT8 in placental development.