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https://hdl.handle.net/2440/97645
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Type: | Journal article |
Title: | Non-esterified fatty acid-induced endoplasmic reticulum stress in cattle cumulus oocyte complexes alters cell metabolism and developmental competence |
Author: | McDowall, M.L. Wu, L.L. Purdey, M. Abell, A.D. Goldys, E.M. MacMillan, K.L. Thompson, J.G. Robker, R.L. |
Citation: | Biology of Reproduction, 2016; 94(1):23 -1-23 -9 |
Publisher: | Society for the Study of Reproduction |
Issue Date: | 2016 |
ISSN: | 0006-3363 1529-7268 |
Statement of Responsibility: | Melanie L. Sutton-McDowall, Linda L.Y. Wu, Malcolm Purdey, Andrew D. Abell, Ewa M. Goldys, Keith L. MacMillan, Jeremy G. Thompson, and Rebecca L. Robker |
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 non-esterified fatty acids (NEFA), known to accumulate within follicular fluid during under- and over-nutrition scenarios, in causing endoplasmic reticulum (ER) stress of in vitro maturated (IVM) cattle cumulus-oocyte 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 24h 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 co-incubation 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-stress mediated process. In contrast, while mitochondrial DNA copy number was recovered in NEFA treated oocytes, oocyte autofluorescence of the respiratory chain co-factor, 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. |
Keywords: | Oocytes Animals Cattle Cinnamates Lactic Acid Thiourea Flavin-Adenine Dinucleotide Glucose Fatty Acids, Nonesterified Heat-Shock Proteins Embryo Culture Techniques Gene Dosage Female Activating Transcription Factor 4 Activating Transcription Factor 6 Cumulus Cells Endoplasmic Reticulum Stress Endoplasmic Reticulum Chaperone BiP |
Description: | Published online before print December 9, 2015. |
Rights: | Copyright 2015 by The Society for the Study of Reproduction. |
DOI: | 10.1095/biolreprod.115.131862 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1077694 http://purl.org/au-research/grants/nhmrc/1044969 |
Published version: | http://dx.doi.org/10.1095/biolreprod.115.131862 |
Appears in Collections: | Aurora harvest 3 Medicine publications |
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