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Type: Journal article
Title: Hyperglycaemia and lipid differentially impair mouse oocyte developmental competence
Author: Wong, S.
Wu, L.
Robker, R.
Thompson, J.
McDowall, M.
Citation: Reproduction, Fertility and Development, 2015; 27(4):583-592
Publisher: CSIRO
Issue Date: 2015
ISSN: 1031-3613
Statement of
Siew L. Wong, Linda L. Wu, Rebecca L. Robker, Jeremy G. Thompson and Melanie L. Sutton McDowall
Abstract: Maternal diabetes and obesity are characterised by elevated blood glucose, insulin and lipids, resulting in upregulation of specific fuel-sensing and stress signalling pathways. Previously, we demonstrated that, separately, upregulation of the hexosamine biosynthetic pathway (HBP; under hyperglycaemic conditions) and endoplasmic reticulum (ER) stress (due to hyperlipidaemia) pathways reduce blastocyst development and alter oocyte metabolism. In order to begin to understand how both glucose and lipid metabolic disruptions influence oocyte developmental competence, in the present study we exposed mouse cumulus–oocyte complexes to hyperglycaemia (30 mM) and/or lipid (40 μM) and examined the effects on embryo development. The presence of glucosamine (GlcN; a hyperglycaemic mimetic) or increased lipid during in vitro maturation severely perturbed blastocyst development (P < 0.05). Hyperglycaemia, GlcN and hyperglycaemia + lipid treatments significantly increased HBP activity, increasing total O-linked glycosylation (O-GlcNAcylation) of proteins (P < 0.0001). All treatments also induced ER stress pathways, indicated by the expression of specific ER stress genes. The expression of genes encoding the HBP enzymes glutamine:fructose-6-phosphate amidotransferase 2 (Gfpt2) and O-linked β-N-acetylglucosaminyltransferase (Ogt) was repressed following lipid treatment (P < 0.001). These findings partially implicate the mechanism of O-GlcNAcylation and ER stress as likely contributors to compromised fertility of obese women.
Keywords: cumulus–oocyte complex; embryo; endoplasmic reticulum stress; hexosamine biosynthesis pathway; hyperlipidemia
Rights: © The author(s)
RMID: 0030025973
DOI: 10.1071/RD14328
Appears in Collections:Paediatrics publications

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