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.

中文翻译：

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甲状腺激素对人着床前胚胎线粒体及代谢的影响

甲状腺激素被认为是哺乳动物代谢率和耗氧量的主要控制者。尽管已经证明补充甲状腺激素可以改善体外牛胚胎发育，但这些影响背后的细胞机制迄今尚不清楚。在这项研究中，我们调查了甲状腺激素在人类植入前胚胎发育中的作用。在存在或不存在 10-7 M 三碘甲状腺原氨酸 (T3) 的情况下培养胚胎直至囊胚期。内细胞团 (ICM) 和滋养外胚层 (TE) 被机械分离并进行 RNAseq 或线粒体 DNA 拷贝数的量化。使用 DESeq（R v3.1.3 上的 v1.16.0）、MeV4.9 和 MitoMiner 4.0v2018 JUN 平台进行分析。我们发现，人类植入前胚胎暴露于 T3 仅对 ICM 细胞（1178 个调节基因 - 11196 个表达基因的 10.5%）的核基因转录产生深远影响，而对 TE 细胞（38 个调节基因）几乎没有影响。 —0.3% 的表达基因）。分析表明，T3 在 ICM 中诱导核糖体和氧化磷酸化活性的转变，因为上调的基因有助于呼吸链的组成和组织以及参与核糖体组装和稳定性的相关辅助因子。此外，许多影响柠檬酸循环能量产生的基因表达减少。我们的研究结果可以解释为什么女性的甲状腺疾病与生育能力下降和不良妊娠结局有关。