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.
Highlights
Thyroid hormones, thyroxine (T4), and its biologically active form triiodothyronine (T3) play vital roles in regulating homeostasis and metabolic rate of human cells and tissues
The analyses suggest that T3 induces in Inner cell mass (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
The results suggest that thyroid hormones affect mitochondrial function in human embryos: stimulate mitochondrial replication and energy production within mitochondria by switching metabolism from glycolytic pathway to more efficient oxidative phosphorylation
Summary
Thyroxine (T4), and its biologically active form triiodothyronine (T3) play vital roles in regulating homeostasis and metabolic rate of human cells and tissues. They are essential for physical and mental development; insufficient production of thyroid hormones before birth or during childhood can lead to reduced growth and mental impairment. Exposure to T3 of human embryonic stem cells (hESCs) derived from the inner cell mass (ICM) of the blastocyst stage embryos and induced pluripotent stem cells triggered expression of multiple genes linked to regulation of gene transcription, cell cycle, morphology, apoptosis, cell viability, and cellular and embryonic development.[7]. We report investigations into the effect of thyroid hormone on the transcriptome of developing human preimplantation embryos and show that ICM and trophectoderm (TE) react differently to T3 exposure. Whereas T3 had a profound effect on gene expression in the ICM, TE cells remained almost unaffected
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