Mouse Blastocysts Pulse Labeled with 14C-Glucosamine: Incorporation and Ultrastructural Analysis

Acey, Roger A.; Hazlett, Linda D.; Dabich, Danica

doi:10.1095/biolreprod16.5.564

Cited by 6 publications

(4 citation statements)

References 25 publications

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“…This is also consistent with nuclear accumulation of 14 C-label grains in embryos that were pulse-labeled with 14 C-glucosamine [22]. Several hundred proteins are modified by O-GlcNAcylation, including transcription factors, kinases, phosphatases, cytoskeletal proteins, and nuclear hormone receptors.…”

Section: O-linked Glycosylation In Early Mouse Embryossupporting

confidence: 77%

Toxic Effects of Hyperglycemia Are Mediated by the Hexosamine Signaling Pathway and O-Linked Glycosylation in Early Mouse Embryos1

Pantaleon

Tan

Kafer

et al. 2010

Biology of Reproduction

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Maternal hyperglycemia is believed to be the metabolic derangement associated with both early pregnancy loss and congenital malformations in a diabetic pregnancy. Using an in vitro model of embryo exposure to hyperglycemia, this study questioned if increased flux through the hexosamine signaling pathway (HSP), which results in increased embryonic O-linked glycosylation (O-GlcNAcylation), underlies the glucotoxic effects of hyperglycemia during early embryogenesis. Mouse zygotes were randomly allocated to culture treatment groups that included no glucose (no flux through HSP), hyperglycemia (27 mM glucose, excess flux), 0.2 mM glucosamine (GlcN) in the absence of glucose (HSP flux alone), and O-GlcNAcylation levels monitored immunohistochemically. The impact of HSP manipulation on the first differentiation in development, blastocyst formation, was assessed, as were apoptosis and cell number in individual embryos. The enzymes regulating O-GlcNAcylation, and therefore hexosamine signaling, are the beta-linked-O-GlcNAc transferase (OGT) and an O-GlcNAc-selective beta-N-acetylglucosaminidase (O-GlcNAcase). Inhibition of these enzymes has a negative impact on blastocyst formation, demonstrating the importance of this signaling system to developmental potential. The ability of the OGT inhibitor benzyl-2-acetamido-2-deoxy-alpha-D-galactopyranoside (BADGP) to reverse the glucotoxic effects of hyperglycemia on these parameters was also sought. Excess HSP flux arising from a hyperglycemic environment or glucosamine supplementation reduced cell proliferation and blastocyst formation, confirming the criticality of this signaling pathway during early embryogenesis. Inhibition of OGT using BADGP blocked the negative impact of hyperglycemia on blastocyst formation, cell number, and apoptosis. Our results suggest that dysregulation of HSP and O-GlcNAcylation is the mechanism by which the embryotoxic effects of hyperglycemia are manifested during preimplantation development.

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Section: O-linked Glycosylation In Early Mouse Embryossupporting

confidence: 77%

Toxic Effects of Hyperglycemia Are Mediated by the Hexosamine Signaling Pathway and O-Linked Glycosylation in Early Mouse Embryos1

Pantaleon

Tan

Kafer

et al. 2010

Biology of Reproduction

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“…Consistent with this distribution, mouse embryos pulselabelled with 14 C-glucosamine display 14 C-label grains in the nucleolus, regions of nucleolar-associated chromatin and the nuclear envelope (Acey et al 1977). This is consistent with observations of predominantly nuclear but also cytoplasmic associated O-GlcNAc in early mouse embryos using antisera that recognize the β-O-GlcNAc linkage (Pantaleon et al 2010).…”

Section: O-glcnacylation In Developmentsupporting

confidence: 85%

Cell Signaling During Mammalian Early Embryo Development

Leese¹,

Brison²

2015

Advances in Experimental Medicine and Biology

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Advances in Experimental Medicine and Biology presents multidisciplinary and dynamic findings in the broad fields of experimental medicine and biology. The wide variety in topics it presents offers readers multiple perspectives on a variety of disciplines including neuroscience, microbiology, immunology, biochemistry, biomedical engineering and cancer research. Advances in Experimental Medicine and Biology has been publishing exceptional works in the field for over 30 years and is indexed in Medline, Scopus, EMBASE, BIOSIS, Biological Abstracts, CSA, Biological Sciences and Living Resources (ASFA-1), and Biological Sciences. The series also provides scientists with up to date information on emerging topics and techniques. This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made. PrefaceInterest in cell signalling in the early embryo extends over the last 30 years, following extensive research on this topic in somatic cells largely in the context of exogenous growth factors and hormones. Thus, Edirisinghe and Wales (1985), working on preimplantation mouse embryos examined the effect of a variety of agents: glucagon, insulin, adrenaline, cAMP, theophylline and caffeine on glucose metabolism while O'Neill (1985), a pioneer in this field, reported that mouse embryos produced platelet-activating factor (PAF) which stimulated blastocyst rates and cell number. Research then focussed largely on peptide growth factors including their origini.e., whether growth factor ligands and/or receptors were produced by the embryo itself or by the female tract (oviduct and uterus), and their cellular effects, which could be autocrine, paracrine or juxtacrine. A number of excellent reviews of these studies were published: e.g., Schultz and Heyner (1993); Kaye (1997); Kane et al. (1997); Hardy and Spanos (2002).In the last few years interest in embryonic signalling has exploded with (i) the increasing use of ART procedures in animals and humans and the need to improve success rates and safety; (ii) ren...

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Section: O-glcnacylation In Developmentsupporting

confidence: 85%

The Role of Hexosamine Biosynthesis and Signaling in Early Development

Pantaleon

2015

Advances in Experimental Medicine and Biology

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Although the culture requirements and the metabolic profile of the preimplantation embryo have been thoroughly investigated since their first successful culture in a defined medium, now more than 50 years ago (Whitten, Nature 177:96, 1956), it is only recently that we have begun to appreciate the impact of the environment on life-course trajectory. The mechanisms involved in how nutrient availability may potentially modulate developmental potential are consequently not well defined. Originally thought of as simple energy substrates and biosynthetic precursors, the currently emerging paradigm suggests that nutrients may act in non-classical roles to impact on developmental potential. This is now an area of considerable activity thanks to pioneering epidemiological studies (Barker et al., BMJ 298:564-7, 1989) that have led to the establishment of the Developmental Origins of Health and Disease (DoHAD) hypothesis and a whole new field of research activity. The period prior to implantation is of particular interest as this has been identified as a critical window of developmental sensitivity to environmental or nutrient stress (Fleming et al., Biol Reprod 71:1046-54, 2004a). This review seeks specifically to explore the pivotal role of glucose in early mouse development and the mechanisms by which it may impact on the cellular functions of the developing embryo. The emerging paradigm suggests that this humble hexose sugar may be at the heart of a rather sophisticated mechanism of cellular control that not only impacts on cellular proliferation and viability in the short term but on cellular memory through to the next generation.

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Mouse Blastocysts Pulse Labeled with 14C-Glucosamine: Incorporation and Ultrastructural Analysis

Cited by 6 publications

References 25 publications

Toxic Effects of Hyperglycemia Are Mediated by the Hexosamine Signaling Pathway and O-Linked Glycosylation in Early Mouse Embryos1

Toxic Effects of Hyperglycemia Are Mediated by the Hexosamine Signaling Pathway and O-Linked Glycosylation in Early Mouse Embryos1

Cell Signaling During Mammalian Early Embryo Development

The Role of Hexosamine Biosynthesis and Signaling in Early Development

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