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

D'Souza, Fiona and Pudakalakatti, Shivanand M and Uppangala, Shubhashree and Honguntikar, Sachin and Salian, Sujith Raj and Kalthur, Guruprasad and Pasricha, Renu and Appajigowda, Divya and Atreya, Hanudatta S and Adiga, Satish Kumar (2016) Unraveling the association between genetic integrity and metabolic activity in pre-implantation stage embryos. In: SCIENTIFIC REPORTS, 6 .

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Official URL: http://dx.doi.org/10.1038/srep37291

Abstract

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.

Item Type: Journal Article
Additional Information: Copy right for this article belongs to the NATURE PUBLISHING GROUP, MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
Department/Centre: Division of Chemical Sciences > NMR Research Centre (Formerly Sophisticated Instruments Facility)
Division of Chemical Sciences > Solid State & Structural Chemistry Unit
Depositing User: Id for Latest eprints
Date Deposited: 30 Dec 2016 07:15
Last Modified: 30 Dec 2016 07:15
URI: http://eprints.iisc.ac.in/id/eprint/55638

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