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The role of Thyroid hormone Transporters Monocarboxylate Transporter 10 (MCT10) and Monocarboxylate Transporter 8 (MCT8) in extravillous trophoblasts.

Choudhury, Juhela (2010)
M.Phil. thesis, University of Birmingham.

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Thyroid hormones (TH) are important for fetal and placental development. Monocarboxylate transporters 8 and 10 (MCT8, 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) Triiodothyronine (T3) effects on gene expression and cell proliferation; 2) the effect of altered MCT8 or MCT10 expression on proliferation and apoptosis; and whether effects were T3-mediated. Methods: 1) Cell proliferation was assessed by the MTT assay at 24-96hrs. Gene expression was assessed by quantitative QPCR (2-48h). 2) MCT8 was down-regulated using siRNA, and MCT8 and MCT10 were over-expressed by plasmid transfection. Effects of altering expression were assessed by MTT assay (Proliferation) and Caspase3/7 activity (Apoptosis). Results: We observed that T3 treatment did not affect HTR-8/SVneo proliferation nor alter the mRNA expressions of TH responsive gene, Connexin43 (Cx43) and the pre-receptor regulators of T3 action, deiodinases 2 and 3 (D2, D3), nor its own transporters, MCT8 and MCT10. However, T3 treatment was observed to decrease the expression of TH receptor β1 (TRβ1) (ANOVA p<0.05). Over-expression of MCT8 or MCT10 reduced cell proliferation by 36% and 29% respectively (ANOVA p<0.05) in the presence of T3. Apoptosis was reduced, independently of T3 treatment, by 24 and 31% (+/- T3 respectively) following overexpression of MCT8, and by 12 and 19% (+/- T3 respectively) following overexpression of MCT10, respectively (ANOVA p<0.005). Conversely, down-regulation of MCT8 resulted in increased apoptosis independently of T3 (p<0.003). Conclusions: HTR-8/SVneo cell proliferation does not change with T3 treatment. In addition, MCT8 and MCT10 may have both T3-dependent (suppress proliferation) and T3-independent (apoptosis) effects in EVTs. This suggests an important role for MCT8 and MCT10 in human placental development.

Type of Work:M.Phil. thesis.
Supervisor(s):Chan, Shiao-yng and Kilby, Mark D
School/Faculty:Colleges (2008 onwards) > College of Medical & Dental Sciences
Department:School of Clinical and Experimental Medicine
Subjects:RC Internal medicine
RJ Pediatrics
Institution:University of Birmingham
ID Code:1195
This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder.
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