Please use this identifier to cite or link to this item: https://biore.bio.bg.ac.rs/handle/123456789/6441
Title: Effects of thyroid hormone on mitochondria and metabolism of human preimplantation embryos
Authors: Noli, Laila
Khorsandi, Shirin E.
Pyle, Angela
Giritharan, Gnanaratnam
Fogarty, Norah
Capalbo, Antonio
Devito, Liani
Jovanović, Vladimir M.
Khurana, Preeti
Rosa, Hannah
Kolundzić, Nikola
Čvoro, Aleksandra 
Niakan, Kathy K.
Malik, Afshan
Foulk, Russell
Heaton, Nigel
Saleh Ardawi, Mohammad
Chinnery, Patrick F.
Ogilvie, Caroline
Khalaf, Yacoub
Ilić, Duško
Keywords: Embryo development;;Mitochondria;;Oxidative phosphorylation;;T3;;Thyroid hormones.
Issue Date: Mar-2020
Rank: M21
Publisher: AlphaMed Press, Inc.
Journal: Stem Cells
Volume: 38
Issue: 3
Start page: 369
End page: 381
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.
URI: https://biore.bio.bg.ac.rs/handle/123456789/6441
DOI: 10.1002/stem.3129
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