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

Lookup NU author(s): Dr Angela Pyle, Professor Patrick Chinnery

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

©2019 The Authors. Stem Cells published by Wiley Periodicals, Inc. on behalf of AlphaMed Press 2019. 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.


Publication metadata

Author(s): Noli L, Khorsandi SE, Pyle A, Giritharan G, Fogarty N, Capalbo A, Devito L, Jovanovic VM, Khurana P, Rosa H, Kolundzic N, Cvoro A, Niakan KK, Malik A, Foulk R, Heaton N, Ardawi MS, Chinnery PF, Ogilvie C, Khalaf Y, Ilic D

Publication type: Article

Publication status: Published

Journal: Stem Cells

Year: 2019

Pages: Epub ahead of print

Online publication date: 28/11/2019

Acceptance date: 13/11/2019

Date deposited: 13/01/2020

ISSN (print): 1066-5099

ISSN (electronic): 1549-4918

Publisher: Wiley-Blackwell

URL: https://doi.org/10.1002/stem.3129

DOI: 10.1002/stem.3129

PubMed id: 31778245


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