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Stem Cells. 2019 Nov 28. doi: 10.1002/stem.3129. [Epub ahead of print]

Effects of thyroid hormone on mitochondria and metabolism of human preimplantation embryos.

Author information

1
Division of Women's and Children's Health, Faculty of Life Sciences and Medicine, King's College London and Assisted Conception Unit, Guy's Hospital, London, UK.
2
Department of Pathological Sciences, Fakeeh College for Medical Sciences, Jeddah, Saudi Arabia.
3
Institute of Liver Studies, King's College Hospital, London, UK.
4
Wellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
5
Nevada Center for Reproductive Medicine, Reno, Nevada.
6
Human Embryo and Stem Cell Laboratory, The Francis Crick Institute, London, UK.
7
Igenomix Italy, via Fermi 1, Marostica, Italy.
8
DAHFMO, Unit of Histology and Medical Embryology, Sapienza, University of Rome, Rome, Italy.
9
Bioinformatics Solution Center and Human Biology Group; Institute for Zoology; Department of Biology, Chemistry and Pharmacy, Freie Universität Berlin, Berlin, Germany.
10
MitoDNA Service Lab, King's College London, London, UK.
11
Center for Bioenergetics, Houston Methodist Research Institute, Houston, Texas.
12
MRC-Mitochondrial Biology Unit and Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
13
Department of Medical and Molecular Genetics, King's College London, London, UK.

Abstract

Thyroid hormones are regarded as the major controllers of metabolic rate and oxygen consumption in mammals. Although it has been demonstrated that thyroid hormone supplementation improves bovine embryo development in vitro, the cellular mechanisms underlying these effects are so far unknown. In this study, we investigated the role of thyroid hormone in development of human preimplantation embryos. Embryos were cultured in the presence or absence of 10-7  M triiodothyronine (T3) till blastocyst stage. Inner cell mass (ICM) and trophectoderm (TE) were separated mechanically and subjected to RNAseq or quantification of mitochondrial DNA copy number. Analyses were performed using DESeq (v1.16.0 on R v3.1.3), MeV4.9 and MitoMiner 4.0v2018 JUN platforms. We found that the exposure of human preimplantation embryos to T3 had a profound impact on nuclear gene transcription only in the cells of ICM (1178 regulated genes-10.5% of 11 196 expressed genes) and almost no effect on cells of TE (38 regulated genes-0.3% of expressed genes). The analyses suggest that T3 induces in ICM a shift in ribosome and oxidative phosphorylation activity, as the upregulated genes are contributing to the composition and organization of the respiratory chain and associated cofactors involved in mitoribosome assembly and stability. Furthermore, a number of genes affecting the citric acid cycle energy production have reduced expression. Our findings might explain why thyroid disorders in women have been associated with reduced fertility and adverse pregnancy outcome. Our data also raise a possibility that supplementation of culture media with T3 may improve outcomes for women undergoing in vitro fertilization.

KEYWORDS:

T3; embryo development; mitochondria; oxidative phosphorylation; thyroid hormone

PMID:
31778245
DOI:
10.1002/stem.3129

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