title: Unraveling the association between genetic integrity and metabolic activity in pre-implantation stage embryos.
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.
authors.affiliation: Division of Clinical Embryology, Centre of Excellence in Clinical Embryology, Kasturba Medical College, Manipal University, Manipal, India.
authors.forename: Fiona
authors.initials: F
authors.lastname: D'Souza
authors.affiliation: NMR Research Centre Indian Institute of Science, Bengaluru, India.|Solid State and Structural Chemistry Unit, Indian Institute of Science, Bengaluru, India.
authors.forename: Shivanand M
authors.initials: SM
authors.lastname: Pudakalakatti
authors.affiliation: Division of Clinical Embryology, Centre of Excellence in Clinical Embryology, Kasturba Medical College, Manipal University, Manipal, India.
authors.forename: Shubhashree
authors.initials: S
authors.lastname: Uppangala
authors.affiliation: Division of Clinical Embryology, Centre of Excellence in Clinical Embryology, Kasturba Medical College, Manipal University, Manipal, India.
authors.forename: Sachin
authors.initials: S
authors.lastname: Honguntikar
authors.affiliation: Division of Clinical Embryology, Centre of Excellence in Clinical Embryology, Kasturba Medical College, Manipal University, Manipal, India.
authors.forename: Sujith Raj
authors.initials: SR
authors.lastname: Salian
authors.affiliation: Division of Clinical Embryology, Centre of Excellence in Clinical Embryology, Kasturba Medical College, Manipal University, Manipal, India.
authors.forename: Guruprasad
authors.initials: G
authors.lastname: Kalthur
authors.affiliation: National Centre For Biological Sciences, TIFR, Bengaluru, India.
authors.forename: Renu
authors.initials: R
authors.lastname: Pasricha
authors.affiliation: National Centre For Biological Sciences, TIFR, Bengaluru, India.
authors.forename: Divya
authors.initials: D
authors.lastname: Appajigowda
authors.affiliation: NMR Research Centre Indian Institute of Science, Bengaluru, India.
authors.forename: Hanudatta S
authors.initials: HS
authors.lastname: Atreya
authors.affiliation: Division of Clinical Embryology, Centre of Excellence in Clinical Embryology, Kasturba Medical College, Manipal University, Manipal, India.
authors.forename: Satish Kumar
authors.initials: SK
authors.lastname: Adiga
mesh_terms: D000818:Animals; D017209:Apoptosis; D001755:Blastocyst / Q000378:metabolism* / Q000473:pathology; D047108:Embryonic Development; D005260:Female; D018507:Gene Expression Regulation, Developmental; D042822:Genomic Instability; D008297:Male; D051379:Mice; D048629:Micronuclei, Chromosome-Defective; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis*
chemical_list: C494827:Bax protein, mouse; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein