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Monocarboxylate transporter 8 modulates the viability and invasive capacity of human placental cells and fetoplacental growth in mice.

Vasilopoulou, E; Loubière, LS; Heuer, H; Trajkovic-Arsic, M; Darras, VM; Visser, TJ; Lash, GE; Whitley, GS; McCabe, CJ; Franklyn, JA; et al. Vasilopoulou, E; Loubière, LS; Heuer, H; Trajkovic-Arsic, M; Darras, VM; Visser, TJ; Lash, GE; Whitley, GS; McCabe, CJ; Franklyn, JA; Kilby, MD; Chan, SY (2013) Monocarboxylate transporter 8 modulates the viability and invasive capacity of human placental cells and fetoplacental growth in mice. PLoS One, 8 (6). ISSN 1932-6203 https://doi.org/10.1371/journal.pone.0065402
SGUL Authors: Whitley, Guy St John

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Abstract

Monocarboxylate transporter 8 (MCT8) is a well-established thyroid hormone (TH) transporter. In humans, MCT8 mutations result in changes in circulating TH concentrations and X-linked severe global neurodevelopmental delay. MCT8 is expressed in the human placenta throughout gestation, with increased expression in trophoblast cells from growth-restricted pregnancies. We postulate that MCT8 plays an important role in placental development and transplacental TH transport. We investigated the effect of altering MCT8 expression in human trophoblast in vitro and in a Mct8 knockout mouse model. Silencing of endogenous MCT8 reduced T3 uptake into human extravillous trophoblast-like cells (SGHPL-4; 40%, P<0.05) and primary cytotrophoblast (15%, P<0.05). MCT8 over-expression transiently increased T3 uptake (SGHPL-4∶30%, P<0.05; cytotrophoblast: 15%, P<0.05). Silencing MCT8 did not significantly affect SGHPL-4 invasion, but with MCT8 over-expression T3 treatment promoted invasion compared with no T3 (3.3-fold; P<0.05). Furthermore, MCT8 silencing increased cytotrophoblast viability (∼20%, P<0.05) and MCT8 over-expression reduced cytotrophoblast viability independently of T3 (∼20%, P<0.05). In vivo, Mct8 knockout reduced fetal:placental weight ratios compared with wild-type controls at gestational day 18 (25%, P<0.05) but absolute fetal and placental weights were not significantly different. The volume fraction of the labyrinthine zone of the placenta, which facilitates maternal-fetal exchange, was reduced in Mct8 knockout placentae (10%, P<0.05). However, there was no effect on mouse placental cell proliferation in vivo. We conclude that MCT8 makes a significant contribution to T3 uptake into human trophoblast cells and has a role in modulating human trophoblast cell invasion and viability. In mice, Mct8 knockout has subtle effects upon fetoplacental growth and does not significantly affect placental cell viability probably due to compensatory mechanisms in vivo.

Item Type: Article
Additional Information: ©2013 Vasilopoulou et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: Analysis of Variance, Animals, Apoptosis, Cell Movement, Cell Proliferation, Cells, Cultured, England, Female, Humans, Membrane Transport Proteins, Mice, Mice, Knockout, Monocarboxylic Acid Transporters, Organ Size, Placenta, Pregnancy, RNA, Small Interfering, Thyroid Hormones, Trophoblasts, Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, IN-VITRO, THYROID-HORMONE TRANSPORT, SUBCLINICAL HYPOTHYROIDISM, EXTRAVILLOUS TROPHOBLASTS, DEIODINASE ACTIVITY, BINDING PROTEIN, NITRIC-OXIDE, EXPRESSION, General Science & Technology, TRIIODOTHYRONINE, MD Multidisciplinary
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) > Vascular (INCCVA)
Journal or Publication Title: PLoS One
Article Number: e65402
ISSN: 1932-6203
Language: eng
Dates:
DateEvent
13 June 2013Published
PubMed ID: 23776477
Web of Science ID: WOS:000320322400022
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/107284
Publisher's version: https://doi.org/10.1371/journal.pone.0065402

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