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

Laila Noli; Shirin E. Khorsandi; Angela Pyle; Gnanaratnam Giritharan; Norah Fogarty; Antonio Capalbo; Liani Devito; Vladimir M. Jovanovic; Preeti Khurana; Hannah Rosa; Nikola Kolundzic; Aleksandra Cvoro; Kathy K. Niakan; Afshan Malik; Russell Foulk; Nigel Heaton; Mohammad Saleh Ardawi; Patrick F. Chinnery; Caroline Ogilvie; Yacoub Khalaf; Dusko Ilic

doi:10.1002/stem.3129

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

Laila Noli, Shirin E. Khorsandi, Angela Pyle, Gnanaratnam Giritharan, Norah Fogarty, Antonio Capalbo, Liani Devito, Vladimir M. Jovanovic, Preeti Khurana, Hannah Rosa, Nikola Kolundzic, Aleksandra Cvoro, Kathy K. Niakan, Afshan Malik, Russell Foulk, Nigel Heaton, Mohammad Saleh Ardawi, Patrick F. Chinnery, Caroline Ogilvie, Yacoub KhalafDusko Ilic^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

20 Citations (Scopus)

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 4.0^{v2018 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.

Original language	English
Journal	Stem Cells
DOIs	https://doi.org/10.1002/stem.3129
Publication status	Published - 1 Jan 2019

Keywords

embryo development
mitochondria
oxidative phosphorylation
T3
thyroid hormone

Access to Document

10.1002/stem.3129

Cite this

Noli, L., Khorsandi, S. E., Pyle, A., Giritharan, G., Fogarty, N., Capalbo, A., Devito, L., Jovanovic, V. M., Khurana, P., Rosa, H., Kolundzic, N., Cvoro, A., Niakan, K. K., Malik, A., Foulk, R., Heaton, N., Ardawi, M. S., Chinnery, P. F., Ogilvie, C., ... Ilic, D. (2019). Effects of thyroid hormone on mitochondria and metabolism of human preimplantation embryos. Stem Cells. https://doi.org/10.1002/stem.3129

@article{a2aed88f2198497a8d05beed4f036af8,

title = "Effects of thyroid hormone on mitochondria and metabolism of human preimplantation embryos",

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 = "embryo development, mitochondria, oxidative phosphorylation, T3, thyroid hormone",

author = "Laila Noli and Khorsandi, {Shirin E.} and Angela Pyle and Gnanaratnam Giritharan and Norah Fogarty and Antonio Capalbo and Liani Devito and Jovanovic, {Vladimir M.} and Preeti Khurana and Hannah Rosa and Nikola Kolundzic and Aleksandra Cvoro and Niakan, {Kathy K.} and Afshan Malik and Russell Foulk and Nigel Heaton and Ardawi, {Mohammad Saleh} and Chinnery, {Patrick F.} and Caroline Ogilvie and Yacoub Khalaf and Dusko Ilic",

year = "2019",

month = jan,

day = "1",

doi = "10.1002/stem.3129",

language = "English",

journal = "Stem Cells",

issn = "1066-5099",

publisher = "AlphaMed Press",

}

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 2019, 'Effects of thyroid hormone on mitochondria and metabolism of human preimplantation embryos', Stem Cells. https://doi.org/10.1002/stem.3129

TY - JOUR

T1 - Effects of thyroid hormone on mitochondria and metabolism of human preimplantation embryos

AU - Noli, Laila

AU - Khorsandi, Shirin E.

AU - Pyle, Angela

AU - Giritharan, Gnanaratnam

AU - Fogarty, Norah

AU - Capalbo, Antonio

AU - Devito, Liani

AU - Jovanovic, Vladimir M.

AU - Khurana, Preeti

AU - Rosa, Hannah

AU - Kolundzic, Nikola

AU - Cvoro, Aleksandra

AU - Niakan, Kathy K.

AU - Malik, Afshan

AU - Foulk, Russell

AU - Heaton, Nigel

AU - Ardawi, Mohammad Saleh

AU - Chinnery, Patrick F.

AU - Ogilvie, Caroline

AU - Khalaf, Yacoub

AU - Ilic, Dusko

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

KW - embryo development

KW - mitochondria

KW - oxidative phosphorylation

KW - T3

KW - thyroid hormone

UR - http://www.scopus.com/inward/record.url?scp=85077360210&partnerID=8YFLogxK

U2 - 10.1002/stem.3129

DO - 10.1002/stem.3129

M3 - Article

C2 - 31778245

AN - SCOPUS:85077360210

SN - 1066-5099

JO - Stem Cells

JF - Stem Cells

ER -

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

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this