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THE ROLE OF THE THYROID HORMONE MONOCARBOXYLATE TRANSPORTER 8 IN HUMAN PLACENTAL DEVELOPMENT

E. Vasilopoulou, L. Loubière, C. McCabe, J. Franklyn, M. Kilby, S. Chan. University of Birmingham, Birmingham, West Midlands, UK

Thyroid hormones (TH) are important for fetoplacental development. Monocarboxylate transporter 8 (MCT8) is a potent plasma membrane TH transporter expressed in the human placenta from 6 weeks of gestation and its expression increases significantly with advancing gestational age. MCT8 expression reduces proliferation in choriocarcinoma-like (JEG-3) cells. In order to investigate the role of MCT8 in human placental development, we transfected human wild type MCT8 or “knocked-down” endogenous MCT8 expression in primary cytotrophoblast cells from term placenta (CTs) and extravillous trophoblast (EVT)-like SGHPL-4 cells followed by 48 h treatment with 0 or 10 nM triiodothyronine (T3). Overexpression of MCT8 decreased viability (MTT assay) of CTs 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 apoptosis (caspase 3/7 activity assay) nor syncytialisation (HCG ELISA). In SGHPL-4s, overexpression of MCT8 increased the effect of T3 on invasion into Matrigel by 2.5-fold compared to vector only control (p<0.05). Downregulation of endogenous MCT8 expression in SGHPL4s reduced apoptosis by 10% both in the presence and absence of T3 (p<0.05). These results indicate that MCT8 acts on trophoblast cells via both T3-dependent and T3-independent mechanisms and that the role of MCT8 varies between term CT cells and EVT-like cells. The fine-tuning of trophoblast viability, apoptosis and invasion is essential for human placental development. These results suggest that MCT8 plays a role in the regulation of trophoblast cellular function.

ANTENATAL MANAGEMENT AND OUTCOME OF FETAL TACHYARRHYTHMIA: A 10-YEAR EXPERIENCE IN A TERTIARY FETAL MEDICINE UNIT

1K. Stewart, 2S. V. Rasiah, 2A. Ewer, 3P. Miller, 3J. Wright, 2M. Kilby. 1University of Birmingham, Birmingham, UK, …

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