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

Fiona D'Souza, Shivanand M. Pudakalakatti, Shubhashree Uppangala, Sachin Honguntikar, Sujith Raj Salian, Guruprasad Kalthur, Renu Pasricha, Divya Appajigowda, Hanudatta S. Atreya, Satish Kumar Adiga

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number37291
JournalScientific Reports
Volume6
DOIs
StatePublished - Nov 17 2016

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Embryonic Structures
Biomarkers
Mammalian Embryo
Chromosomal Instability
Thymine
Isoleucine
DNA
Valine
Metabolic Networks and Pathways
Pyruvic Acid
Proline
Alanine
Mental Competency
Lysine
Lactic Acid
Magnetic Resonance Spectroscopy
Apoptosis
Glucose

ASJC Scopus subject areas

  • General

Cite this

D'Souza, F., Pudakalakatti, S. M., Uppangala, S., Honguntikar, S., Salian, S. R., Kalthur, G., ... Adiga, S. K. (2016). Unraveling the association between genetic integrity and metabolic activity in pre-implantation stage embryos. Scientific Reports, 6, [37291]. https://doi.org/10.1038/srep37291

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

In: Scientific Reports, Vol. 6, 37291, 17.11.2016.

Research output: Contribution to journalArticle

D'Souza, F, Pudakalakatti, SM, Uppangala, S, Honguntikar, S, Salian, SR, Kalthur, G, Pasricha, R, Appajigowda, D, Atreya, HS & Adiga, SK 2016, 'Unraveling the association between genetic integrity and metabolic activity in pre-implantation stage embryos', Scientific Reports, vol. 6, 37291. https://doi.org/10.1038/srep37291
D'Souza F, Pudakalakatti SM, Uppangala S, Honguntikar S, Salian SR, Kalthur G et al. Unraveling the association between genetic integrity and metabolic activity in pre-implantation stage embryos. Scientific Reports. 2016 Nov 17;6. 37291. https://doi.org/10.1038/srep37291
D'Souza, Fiona ; Pudakalakatti, Shivanand M. ; Uppangala, Shubhashree ; Honguntikar, Sachin ; Salian, Sujith Raj ; Kalthur, Guruprasad ; Pasricha, Renu ; Appajigowda, Divya ; Atreya, Hanudatta S. ; Adiga, Satish Kumar. / Unraveling the association between genetic integrity and metabolic activity in pre-implantation stage embryos. In: Scientific Reports. 2016 ; Vol. 6.
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