Disrupted blastocoele formation reveals a critical developmental role for long-chain acyl-CoA dehydrogenase

Paul S. Berger, Philip A. Wood

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Long-chain acyl-CoA dehydrogenase (LCAD) deficiency has not been found in human patients. There has been an LCAD deficient (LCAD-/-) mouse model developed via gene targeting strategies that has gestational loss as a part of its phenotype. We tested the hypothesis that LCAD deficiency disrupts normal embryonic development and explains at least in part the gestational loss in the mouse and may suggest a mechanism to explain the lack of any human patients with this inherited enzyme deficiency. We cultured and evaluated embryos with three different genotypes: LCAD+/+, LCAD+/-, and LCAD-/-. We found a significantly increased rate of death (P<0.012) in LCAD-/- embryos at the morula-to-blastocyst conversion indicating a deficient ability to complete the development of a blastocoele and formation of a blastocyst. Furthermore, we hypothesized that we could rescue LCAD-/- embryos in culture by supplying excess fatty acids of chain-lengths that could be readily oxidized by them despite their inherited enzyme deficiency. We were unable, however, to demonstrate any rescue by supplementing the culture medium with fatty acids of a wide-range of chain-lengths. Therefore, overall we demonstrated a severely deficient capacity for LCAD-/- embryos to develop past the morula stage with intermediate rates of development found in the LCAD+/- embryos as compared to the LCAD+/+ embryos. Furthermore, we were unable to rescue the LCAD-/- embryos with any fatty acid supplementation.

Original languageEnglish (US)
Pages (from-to)266-272
Number of pages7
JournalMolecular Genetics and Metabolism
Volume82
Issue number4
DOIs
StatePublished - Aug 2004

Bibliographical note

Funding Information:
This work was supported by NIH Grants RO1-RR-02599 and T-32 RR07003. We thank Larry W. Johnson for his assistance in developing the embryo culture system; and Robert Hardy and Jeff Carroll for their assistance with methods for preparing the albumin-conjugated fatty acids.

Keywords

  • Blastocoele formation
  • Blastocyst
  • Fatty acids
  • Long-chain acyl-CoA dehydrogenase (LCAD)
  • Preimplantation development
  • β-oxidation

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