Association between amino acid turnover and chromosome aneuploidy during human preimplantation embryo development in vitro

Picton, Helen M., Elder, Kay, Houghton, Franchesca D., Hawkhead, Judith A., Rutherford, Anthony J., Hogg, Jan E., Leese, Henry J. and Harris, Sarah E. (2010) Association between amino acid turnover and chromosome aneuploidy during human preimplantation embryo development in vitro. Molecular Human Reproduction, 16 (8), 557-569. (doi:10.1093/molehr/gaq040).

Abstract

This study investigated the relationship between human preimplantation embryo metabolism and aneuploidy rates during development in vitro. 188 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 (HPLC). Embryos were either fixed for interphase fluorescent in situ hybridisation (FISH) 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 day 2-3 of culture. By day 3-4 the profiles of serine, leucine and lysine differed between uniformly euploid vs. aneuploid embryos. Gender significantly (P<0.05) affected the metabolism of tryptophan, leucine and asparagine by cleavage-staged embryos. Pronucleate zygotes had a significantly higher proportion of active:inactive mitochondria compared to cleavage-staged 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.

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Contributors

Author: Franchesca D. Houghton

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