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The role of thyroid hormones in placental development and the importance of the thyroid hormone transporter MCT8

Vasilopoulou, Elisavet (2010)
Ph.D. thesis, University of Birmingham.

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Abstract

Thyroid hormones (THs) are important for fetoplacental development. Human intrauterine growth restriction (IUGR) is associated with malplacentation and reduced fetal circulating concentration of THs. The expression of the plasma membrane TH transporters MCT8, MCT10, LAT1, LAT2, OATP1A2 and OATP4A1 was characterised in human placental biopsies across gestation. The protein expression of MCT8 was increased in samples from severe IUGR compared with normal pregnancies. In vitro, triiodothyronine (T\(_3\)) decreased survival and increased apoptosis of IUGR compared with normal cytotrophoblasts, which was associated with increased MCT8 expression. In normal cytotrophoblasts, MCT8 upregulation decreased survival, whilst MCT8 silencing increased survival independently of T\(_3\). In the extravillous trophoblast-like cell line, SGHPL-4, T\(_3\) resulted in a significant increase in cell invasion when MCT8 was upregulated. Contrary to cytotrophoblasts, silencing MCT8 decreased apoptosis in SGHPL-4s independently of T\(_3\). In mice, fetal to placental weight ratio was decreased in male MCT8-null compared with wild-type embryos. These findings support the hypothesis that THs have an important role in fetoplacental development and that IUGR is associated with changes in TH transport and responsiveness of the placenta. Furthermore, they highlight the importance of MCT8, which impacts on placental cells via both T\(_3\)- dependent and independent mechanisms.

Type of Work:Ph.D. thesis.
Supervisor(s):Chan, Shiao and Kilby, Mark D
School/Faculty:Colleges (2008 onwards) > College of Medical & Dental Sciences
Department:School of Clinical and Experimental Medicine
Subjects:RG Gynecology and obstetrics
QP Physiology
Institution:University of Birmingham
ID Code:1146
This unpublished thesis/dissertation is copyright of the author and/or third parties.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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