title: Association between amino acid turnover and chromosome aneuploidy during human preimplantation embryo development in vitro.
abstract: This study investigated the relationship between human preimplantation embryo metabolism and aneuploidy rates during development in vitro. One hundred and eighty-eight fresh and cryopreserved embryos from 59 patients (33.9 +/- 0.6 years) were cultured for 2-5 days. The turnover of 18 amino acids was measured in spent media by high-performance liquid chromatography. Embryos were either fixed for interphase fluorescent in situ hybridization analysis of chromosomes 13, 18, 19, 21, X or Y, or were assayed for mitochondrial activity. Amino acid turnover was different (P < 0.05) between stage-matched fresh and cryopreserved embryos due to blastomere loss following warming. The proportion of embryos with aneuploid cells increased as cell division progressed from pronucleate- (23%) to late cleavage stages (50-70%). Asparagine, glycine and valine turnover was significantly different between uniformly genetically normal and uniformly abnormal embryos on Days 2-3 of culture. By Days 3-4, the profiles of serine, leucine and lysine differed between uniformly euploid versus aneuploid embryos. Gender significantly (P < 0.05) affected the metabolism of tryptophan, leucine and asparagine by cleavage-stage embryos. Pronucleate zygotes had a significantly higher proportion of active:inactive mitochondria compared with cleavage-stage embryos. Furthermore, mitochondrial activity was correlated (P < 0.05) with altered aspartate and glutamine turnover. These results demonstrate the association between the metabolism, cytogenetic composition and health of human embryos in vitro.
authors.affiliation: Division of Reproduction and Early Development, Leeds Institute for Genetics, Health and Therapeutics, University of Leeds, Leeds, UK. h.m.picton@leeds.ac.uk
authors.forename: Helen M
authors.initials: HM
authors.lastname: Picton
authors.forename: Kay
authors.initials: K
authors.lastname: Elder
authors.forename: Franchesca D
authors.initials: FD
authors.lastname: Houghton
authors.forename: Judith A
authors.initials: JA
authors.lastname: Hawkhead
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Rutherford
authors.forename: Jan E
authors.initials: JE
authors.lastname: Hogg
authors.forename: Henry J
authors.initials: HJ
authors.lastname: Leese
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Harris
mesh_terms: D000328:Adult; D000596:Amino Acids / Q000378:metabolism*; D000782:Aneuploidy; D002851:Chromatography, High Pressure Liquid; D015925:Cryopreservation; D004622:Embryo, Mammalian; D047108:Embryonic Development / Q000235:genetics / Q000502:physiology*; D005260:Female; D006801:Humans; D008423:Maternal Age; D011247:Pregnancy; D012737:Sex Factors
chemical_list: D000596:Amino Acids