Role of methionine adenosyltransferase 2A in bovine preimplantation development and its associated genomic regions

Ikeda, Shuntaro; Kawahara-Miki, Ryouka; Iwata, Hisataka; Sugimoto, Miki; Kume, Shinji

doi:10.1038/s41598-017-04003-1

Cited by 15 publications

(13 citation statements)

References 52 publications

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“…In this context, it is interesting to point out that a homozygous Mat2a knockout mutation results in embryonic lethality in mice (International Mouse Phenotyping Consortium [IMPC]). Furthermore, chemical inhibition of bovine MAT2A enzyme in cultured bovine pre-implantation embryos also reduced blastocyst development ( Ikeda et al., 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Methylation of Structured RNA by the m6A Writer METTL16 Is Essential for Mouse Embryonic Development

et al. 2018

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SummaryInternal modification of RNAs with N6-methyladenosine (m6A) is a highly conserved means of gene expression control. While the METTL3/METTL14 heterodimer adds this mark on thousands of transcripts in a single-stranded context, the substrate requirements and physiological roles of the second m6A writer METTL16 remain unknown. Here we describe the crystal structure of human METTL16 to reveal a methyltransferase domain furnished with an extra N-terminal module, which together form a deep-cut groove that is essential for RNA binding. When presented with a random pool of RNAs, METTL16 selects for methylation-structured RNAs where the critical adenosine is present in a bulge. Mouse 16-cell embryos lacking Mettl16 display reduced mRNA levels of its methylation target, the SAM synthetase Mat2a. The consequence is massive transcriptome dysregulation in ∼64-cell blastocysts that are unfit for further development. This highlights the role of an m6A RNA methyltransferase in facilitating early development via regulation of SAM availability.

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Section: Discussionmentioning

confidence: 99%

Methylation of Structured RNA by the m6A Writer METTL16 Is Essential for Mouse Embryonic Development

et al. 2018

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“…Importantly, this loss in developmental potential coincides with the increase in SAM synthesis that occurs following compaction (Menezo et al 1989), suggesting a requirement for appropriate metabolite availability at the time of EGA. A requirement for SAM is also evidenced by studies that demonstrate that inhibition of MAT2A, which catalyses the formation of SAM, significantly reduces bovine and mouse blastocyst development and cell number and increases apoptosis (Ikeda et al 2017, Sun et al 2018. Conversely, SAM supplementation during bovine embryo culture enhances hatching, accompanied by significant alterations in the global DNA methylation landscape (Shojaei Saadi et al 2016).…”

Section: Metabolic Regulators Of Acetylation and Methylationmentioning

confidence: 99%

Mitochondria in early development: linking the microenvironment, metabolism and the epigenome

Harvey¹

2019

Reproduction

112

101

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Mitochondria, originally of bacterial origin, are highly dynamic organelles that have evolved a symbiotic relationship within eukaryotic cells. Mitochondria undergo dynamic, stage-specific restructuring and redistribution during oocyte maturation and preimplantation embryo development, necessary to support key developmental events. Mitochondria also fulfil a wide range of functions beyond ATP synthesis, including the production of intracellular reactive oxygen species and calcium regulation, and are active participants in the regulation of signal transduction pathways. Communication between not only mitochondria and the nucleus, but also with other organelles, is emerging as a critical function which regulates preimplantation development. Significantly, perturbations and deficits in mitochondrial function manifest not only as reduced quality and/or poor oocyte and embryo development but contribute to post-implantation failure, long-term cell function and adult disease. A growing body of evidence indicates that altered availability of metabolic co-factors modulate the activity of epigenetic modifiers, such that oocyte and embryo mitochondrial activity and dynamics have the capacity to establish long-lasting alterations to the epigenetic landscape. It is proposed that preimplantation embryo development may represent a sensitive window during which epigenetic regulation by mitochondria is likely to have significant short- and long-term effects on embryo, and offspring, health. Hence, mitochondrial integrity, communication and metabolism are critical links between the environment, the epigenome and the regulation of embryo development.

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“…Bovine 1‐cell embryos at 20 hr post‐insemination (hpi) and produced in vitro as described elsewhere (Ikeda, Kawahara‐Miki, Iwata, Sugimoto, & Kume, ) were treated with pronase solution (0.5% [w/v] in PBS) to remove the zona pellucida. The zona‐free 1‐cell embryos were individually allocated to a well‐of‐the‐well system (Vajta et al, ) using the LinKID micro25 culture dish (Dai Nippon Printing, Tokyo, Japan) with 50 μl of modified synthetic oviduct fluid (mSOF) and cultured until 70 hpi.…”

Section: Methodsmentioning

confidence: 99%

“…Bovine 1-cell embryos at 20 hr post-insemination (hpi) and produced in vitro as described elsewhere (Ikeda, Kawahara-Miki, Iwata, Sugimoto, & Kume, 2017) were treated with pronase solution (0.5% [w/v] in PBS)…”

Section: Aggregation Of Cell Lines With Bovine Embryosmentioning

confidence: 99%

Long‐term culture of undifferentiated spermatogonia isolated from immature and adult bovine testes

Suyatno

Kitamura

Ikeda

et al. 2018

Molecular Reproduction Devel

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Undifferentiated spermatogonia eventually differentiate in the testis to produce haploid sperm. Within this cell population, there is a small number of spermatogonial stem cells (SSCs). SSCs are rare cells in the testis, and their cellular characteristics are poorly understood. Establishment of undifferentiated cell line would provide an indispensable tool for studying their biological nature and spermiogenesis/spermatogenesis in vitro. However, there have been few reports on the long-term culture of undifferentiated spermatogonia in species other than rodents. Here, we report the derivation and long-term in vitro culture of undifferentiated spermatogonia cell lines from immature and adult bovine testes. Cell lines from immature testes were maintained in serum-free culture conditions in the presence of glial-cell-line-derived neurotropic factor (GDNF) and bovine leukemia inhibitory factor (bLIF). These cell lines have embryonic stem (ES)-like cell morphology, express pluripotent-stem-cell-specific and germ-cell-specific markers at the protein and mRNA levels, and contributed to the inner cell mass (ICM) of embryos in the blastocyst stage. Meanwhile, cell lines established from adult testes were maintained in low-serum media in the presence of 6-bromoindirubin-3'-oxime (BIO). These cell lines have characteristics resembling those of previously reported male mouse germ cell lines as confirmed by their botryoidally aggregated morphology, as well as the expression of germ-cell-specific markers and pluripotent stem cell markers. These findings could be useful for the development of long-term culture of undifferentiated spermatogonia, which could aid in conservation of species and improvement of livestock production through genome editing technology.

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Role of methionine adenosyltransferase 2A in bovine preimplantation development and its associated genomic regions

Cited by 15 publications

References 52 publications

Methylation of Structured RNA by the m6A Writer METTL16 Is Essential for Mouse Embryonic Development

Methylation of Structured RNA by the m6A Writer METTL16 Is Essential for Mouse Embryonic Development

Mitochondria in early development: linking the microenvironment, metabolism and the epigenome

Long‐term culture of undifferentiated spermatogonia isolated from immature and adult bovine testes

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