Association between amino acid turnover and chromosome aneuploidy during human preimplantation embryo development in vitro.
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.
Picton
Helen M
HM
Division of Reproduction and Early Development, Leeds Institute for Genetics, Health and Therapeutics, University of Leeds, Leeds, UK. h.m.picton@leeds.ac.uk
Elder
Kay
K
Houghton
Franchesca D
FD
Hawkhead
Judith A
JA
Rutherford
Anthony J
AJ
Hogg
Jan E
JE
Leese
Henry J
HJ
Harris
Sarah E
SE
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
D000596:Amino Acids