Assessing embryo viability by measurement of amino acid turnover

Sturmey, Roger G.; Brison, Daniel R.; Leese, Henry J.

doi:10.1016/s1472-6483(10)60234-9

Cited by 84 publications

(47 citation statements)

References 97 publications

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“…Our results suggest that genetic instability in the embryos triggers the uptake of energy substrates and amino acids to facilitate the DNA repair process. Amino acids are precursors for protein and nucleotide synthesis383940, and regulate metabolism in preimplantation embryos41.…”

Section: Discussionmentioning

confidence: 99%

Unraveling the association between genetic integrity and metabolic activity in pre-implantation stage embryos

D’Souza

Pudakalakatti

Uppangala

et al. 2016

Sci Rep

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Early development of certain mammalian embryos is protected by complex checkpoint systems to maintain the genomic integrity. Several metabolic pathways are modulated in response to genetic insults in mammalian cells. The present study investigated the relationship between the genetic integrity, embryo metabolites and developmental competence in preimplantation stage mouse embryos with the aim to identify early biomarkers which can predict embryonic genetic integrity using spent medium profiling by NMR spectroscopy. Embryos carrying induced DNA lesions (IDL) developed normally for the first 2.5 days, but began to exhibit a developmental delay at embryonic day 3.5(E3.5) though they were morphologically indistinguishable from control embryos. Analysis of metabolites in the spent medium on E3.5 revealed a significant association between pyruvate, lactate, glucose, proline, lysine, alanine, valine, isoleucine and thymine and the extent of genetic instability observed in the embryos on E4.5. Further analysis revealed an association of apoptosis and micronuclei frequency with P53 and Bax transcripts in IDL embryos on the E4.5 owing to delayed induction of chromosome instability. We conclude that estimation of metabolites on E3.5 in spent medium may serve as a biomarker to predict the genetic integrity in pre-implantation stage embryos which opens up new avenues to improve outcomes in clinical IVF programs.

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Section: Discussionmentioning

confidence: 99%

Unraveling the association between genetic integrity and metabolic activity in pre-implantation stage embryos

D’Souza

Pudakalakatti

Uppangala

et al. 2016

Sci Rep

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“…This area has been comprehensively reviewed by Sturmey et al (2008) and a brief account only is given here. Amino acids are now added routinely to human embryo culture media but this was not the case during the early years of IVF.…”

Section: Amino Acidsmentioning

confidence: 99%

Metabolism of the preimplantation embryo: 40 years on

Leese¹

2012

Reproduction

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299

201

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This review considers how our understanding of preimplantation embryo metabolism has progressed since the pioneering work on this topic in the late 1960s and early 1970s. Research has been stimulated by a desire to understand how metabolic events contribute to the development of the zygote into the blastocyst, the need for biomarkers of embryo health with which to improve the success of assisted conception technologies, and latterly by the ‘Developmental Origins of Health and Disease’ (DOHaD) concept. However, arguably, progress has not been as great as it might have been due to methodological difficulties in working with tiny amounts of tissue and the low priority assigned to fundamental research on fertility and infertility, with developments driven more by technical than scientific advances. Nevertheless, considerable progress has been made in defining the roles of the traditional nutrients: pyruvate, glucose, lactate, and amino acids; originally considered as energy sources and biosynthetic precursors, but now recognized as having multiple, overlapping functions. Other nutrients; notably lipids, are beginning to attract the attention they deserve. The pivotal role of mitochondria in early embryo development and the DOHaD concept, and in providing a cellular focus for metabolic events is now recognized. Some unifying ideas are discussed; namely ‘stress–response models’ and the ‘quiet embryo hypothesis’; the latter aiming to relate the metabolism of individual preimplantation embryos to their subsequent viability. The review concludes by updating the state of knowledge of preimplantation embryo metabolism in the early 1970s and listing some future research questions.

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“…Mammalian preimplantation embryo metabolism follows a widely accepted general pattern, which has been extensively reviewed [7]–[9]. During the cleavage stages, early embryos predominantly consume pyruvate, which is largely oxidised to CO 2 [10] but, at least in the human, may also be converted to lactate [11].…”

Section: Introductionmentioning

confidence: 99%

A Simple Approach for COnsumption and RElease (CORE) Analysis of Metabolic Activity in Single Mammalian Embryos

et al. 2013

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Non-invasive assay of the consumption and release of metabolites by individual human embryos could allow selection at the cleavage stage of development and facilitate Single Embryo Transfer in clinical IVF but will require simple, high throughput, sensitive methods applicable to small volume samples.A rapid, simple, non-invasive method has therefore been devised using a standard fluorescence plate reader, and used to measure the consumption of pyruvate and glucose, and release of lactate by single bovine embryos at all stages of preimplantation development in culture; amino acid profiles have been determined using HPLC.Early embryos with an ‘intermediate’ level (6.14±0.27 pmol/embryo/h) of pyruvate uptake were associated with the highest rate (68.3%) of blastocyst development indicating that a mid “optimum” range of pyruvate consumption correlates with high viability in this bovine model.

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Assessing embryo viability by measurement of amino acid turnover

Cited by 84 publications

References 97 publications

Unraveling the association between genetic integrity and metabolic activity in pre-implantation stage embryos

Unraveling the association between genetic integrity and metabolic activity in pre-implantation stage embryos

Metabolism of the preimplantation embryo: 40 years on

A Simple Approach for COnsumption and RElease (CORE) Analysis of Metabolic Activity in Single Mammalian Embryos

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