Nonesterified fatty acid-induced endoplasmic reticulum stress in cattle cumulus oocyte complexes alters cell metabolism and developmental competence

Melanie L. Sutton-McDowall*, Linda L Y Wu, Malcolm Purdey, Andrew D. Abell, Ewa M. Goldys, Keith L. MacMillan, Jeremy G. Thompson, Rebecca L. Robker

*Corresponding author for this work

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Reduced oocyte quality has been associated with poor fertility of high-performance dairy cows during peak lactation, due to negative energy balance. We examined the role of nonesterified fatty acids (NEFAs), known to accumulate within follicular fluid during under- and overnutrition scenarios, in causing endoplasmic reticulum (ER) stress of in vitro maturated cattle cumulusoocyte complexes (COCs). NEFA concentrations were: palmitic acid (150 μM), oleic acid (200 μM), and steric acid (75 μM). Abattoir-derived COCs were randomly matured for 24 h in the presence of NEFAs and/or an ER stress inhibitor, salubrinal. Total and hatched blastocyst yields were negatively impacted by NEFA treatment compared with controls, but this was reversed by salubrinal. ER stress markers, activating transcription factor 4 (Atf4) and heat shock protein 5 (Hspa5), but not Atf6, were significantly up-regulated by NEFA treatment within whole COCs but reversed by coincubation with salubrinal. Likewise, glucose uptake and lactate production, measured in spent medium samples, showed a similar pattern, suggesting that cumulus cell metabolism is sensitive to NEFAs via an ER stressmediated process. In contrast, while mitochondrial DNA copy number was recovered in NEFA-treated oocytes, oocyte autofluorescence of the respiratory chain cofactor, FAD, was lower following NEFA treatment of COCs, and this was not reversed by salubrinal, suggesting the negative impact was via reduced mitochondrial function. These results reveal the significance of NEFA-induced ER stress on bovine COC developmental competence, revealing a potential therapeutic target for improving oocyte quality during peak lactation.

Original languageEnglish
Article number23
Pages (from-to)1-9
Number of pages9
JournalBiology of Reproduction
Volume94
Issue number1
DOIs
Publication statusPublished - 1 Jan 2016

Keywords

  • Cattle
  • Cumulus oocyte complex
  • Endoplasmic reticulum stress
  • Lipids
  • Nonesterified fatty acids

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    ARC CoE Nanoscale BioPhotonics (CNBP) (RAAP)

    Piper, J., Goldys, E., Packer, N. & Jin, D.

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