Mining RNAseq data reveals dynamic metaboloepigenetic profiles in human, mouse and bovine pre-implantation embryos

Milazzotto, Marcella Pécora; Noonan, Michael; Ferraz, Marcia de Almeida Monteiro Melo

doi:10.1016/j.isci.2022.103904

Cited by 9 publications

(5 citation statements)

References 106 publications

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“…The pyruvate metabolism occupies a central position in the blastocyst energy generation as it connects two of the most important pathways in this stage, the glycolytic pathway, and the TCA cycle. Also, TCA cycle was recently described as an important regulator of the embryonic epigenome 33 . In this work, we address the consequences of manipulating the pyruvate metabolism during the embryo development and propose a comprehensive profiling of embryonic metabolic, epigenetic, and molecular adaptation to these alterations.…”

Section: Discussionmentioning

confidence: 99%

Adaptative response to changes in pyruvate metabolism on the epigenetic landscapes and transcriptomics of bovine embryos

Junior

Ispada

Santos

et al. 2023

Sci Rep

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The epigenetic reprogramming that occurs during the earliest stages of embryonic development has been described as crucial for the initial events of cell specification and differentiation. Recently, the metabolic status of the embryo has gained attention as one of the main factors coordinating epigenetic events. In this work, we investigate the link between pyruvate metabolism and epigenetic regulation by culturing bovine embryos from day 5 in the presence of dichloroacetate (DCA), a pyruvate analog that increases the pyruvate to acetyl-CoA conversion, and iodoacetate (IA), which inhibits the glyceraldehyde-3-phosphate dehydrogenase (GAPDH), leading to glycolysis inhibition. After 8 h of incubation, both DCA and IA-derived embryos presented higher mitochondrial membrane potential. Nevertheless, in both cases, lower levels of acetyl-CoA, ATP-citrate lyase and mitochondrial membrane potential were found in blastocysts, suggesting an adaptative metabolic response, especially in the DCA group. The metabolic alteration found in blastocysts led to changes in the global pattern of H3K9 and H3K27 acetylation and H3K27 trimethylation. Transcriptome analysis revealed that such alterations resulted in molecular differences mainly associated to metabolic processes, establishment of epigenetic marks, control of gene expression and cell cycle. The latter was further confirmed by the alteration of total cell number and cell differentiation in both groups when compared to the control. These results corroborate previous evidence of the relationship between the energy metabolism and the epigenetic reprogramming in preimplantation bovine embryos, reinforcing that the culture system is decisive for precise epigenetic reprogramming, with consequences for the molecular control and differentiation of cells.

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Section: Discussionmentioning

confidence: 99%

Adaptative response to changes in pyruvate metabolism on the epigenetic landscapes and transcriptomics of bovine embryos

Junior

Ispada

Santos

et al. 2023

Sci Rep

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“…In addition to the methods described above, pre-implantation bovine embryos have been studied using a variety of other tools too (Table 10). Ribosome profile High-resolution ribosome fractionation, polysome profiling, RNA-seq [198] DNA methylation landscape Anti-5-methylcytosine (5-MeC) antibody, methylation-sensitive high-resolution melting analysis (MS-HRM), bisulfite sequencing [75,[242][243][244][245][246][247][248] mRNA localization In situ hybridization [63,80,249,250] Chromosomal abnormalities 5% Giemsa staining (1250× magnification) [251] Automation/artificial intelligence (AI)-based microscopy Use of genetic algorithms, artificial neural networks, automatic feature extraction from images and supervised learning to formulate AI-based computer-assisted scoring systems (CASS)/predictive models [1,[252][253][254][255][256] Gene knockdown Cytosine base editing, CRISPR/Cas-9 gene editing, siRNA-mediated gene knockdown [79,182,196,197,257] Characterization of extracellular vesicles Nanoparticle tracking analysis, electron microscopy, small RNA sequencing [258][259][260] Multi-omics approaches Integrating transcriptomic and epigenetic data and integrating metabolomics and epigenetic data [261,262]…”

Section: Less Commonly Used Toolsmentioning

confidence: 99%

Pre-Implantation Bovine Embryo Evaluation—From Optics to Omics and Beyond

Rabel

Marchioretto

Bangert

et al. 2023

Animals

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Approximately 80% of the ~1.5 million bovine embryos transferred in 2021 were in vitro produced. However, only ~27% of the transferred IVP embryos will result in live births. The ~73% pregnancy failures are partly due to transferring poor-quality embryos, a result of erroneous stereomicroscopy-based morphological evaluation, the current method of choice for pre-transfer embryo evaluation. Numerous microscopic (e.g., differential interference contrast, electron, fluorescent, time-lapse, and artificial-intelligence-based microscopy) and non-microscopic (e.g., genomics, transcriptomics, epigenomics, proteomics, metabolomics, and nuclear magnetic resonance) methodologies have been tested to find an embryo evaluation technique that is superior to morphologic evaluation. Many of these research tools can accurately determine embryo quality/viability; however, most are invasive, expensive, laborious, technically sophisticated, and/or time-consuming, making them futile in the context of in-field embryo evaluation. However accurate they may be, using complex methods, such as RNA sequencing, SNP chips, mass spectrometry, and multiphoton microscopy, at thousands of embryo production/collection facilities is impractical. Therefore, future research is warranted to innovate field-friendly, simple benchtop tests using findings already available, particularly from omics-based research methodologies. Time-lapse monitoring and artificial-intelligence-based automated image analysis also have the potential for accurate embryo evaluation; however, further research is warranted to innovate economically feasible options for in-field applications.

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“…Although the preferred metabolic pathways to produce energy are variable between species (Milazzotto et al 2022b), one thing is clear: embryos are dynamic and present high ability to adjust their metabolism to the environment surrounding them. The concept of embryo plasticity has been vastly explored, and modifications in temperature, osmolality, composition, and pH of the culture media have been extensively investigated (Coticchio et al 2021).…”

Section: F17mentioning

confidence: 99%

“…As a result, basic knowledge is limited, but we know that early mammalian gametes and embryos present a very peculiar metabolism in comparison with somatic/ differentiated cells. In different species, metabolic requirements vary according to the developmental stage of the embryo, particularly during first cleavages and up to the blastocyst stage (Krisher et al 2015, Milazzotto et al 2022b. During this peri-implantation stage, there is a remarkable shift in the way cells utilize metabolites to produce the energy and the substrates that will be used for cell division, growth, and differentiation.…”

Section: Introductionmentioning

confidence: 99%

DOHaD: A Menagerie of Adaptations and Perspectives: The interplay between early embryo metabolism and mitoepigenetic programming of development

2023

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Initially perceived simply as an ATP producer, mitochondria also participate in a wide range of other cellular functions. Mitochondrial communication with the nucleus, as well as signaling to other cellular compartments is critical to cell homeostasis. Therefore, during early mammalian development, mitochondrial function is reported as a key element for survival. Any mitochondrial dysfunction may reflect in poor oocyte quality and may impair embryo development with possible long-lasting consequences to cell functions and the overall embryo phenotype. Growing evidence suggests that the availability of metabolic modulators can alter the landscape of epigenetic modifications in the nuclear genome providing an important layer for the regulation of nuclear-encoded gene expression. However, whether mitochondria could also be subjected to such similar epigenetic alterations and the mechanisms involved remain largely obscure and controversial. Mitochondrial epigenetics, also known as ‘mitoepigenetics’ is an intriguing regulatory mechanism in mitochondrial DNA (mtDNA)-encoded gene expression. In this review, we summarized the recent advances in mitoepigenetics, with a special focus on mtDNA methylation in reproductive biology and preimplantation development. A better comprehension of the regulatory role of mitoepigenetics will help the understanding of mitochondrial dysfunction and provide novel strategies for in vitro production systems and assisted reproduction technologies, as well as prevent metabolic-related stress and diseases.

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Mining RNAseq data reveals dynamic metaboloepigenetic profiles in human, mouse and bovine pre-implantation embryos

Cited by 9 publications

References 106 publications

Adaptative response to changes in pyruvate metabolism on the epigenetic landscapes and transcriptomics of bovine embryos

Adaptative response to changes in pyruvate metabolism on the epigenetic landscapes and transcriptomics of bovine embryos

Pre-Implantation Bovine Embryo Evaluation—From Optics to Omics and Beyond

DOHaD: A Menagerie of Adaptations and Perspectives: The interplay between early embryo metabolism and mitoepigenetic programming of development

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