title: Nonesterified Fatty Acid-Induced Endoplasmic Reticulum Stress in Cattle Cumulus Oocyte Complexes Alters Cell Metabolism and Developmental Competence.
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 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 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 stress-mediated 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.
authors.affiliation: Australian Research Council Centre of Excellence for Nanoscale BioPhotonics Robinson Research Institute, School of Medicine, The University of Adelaide, Adelaide, South Australia, Australia Institute of Photonics and Advanced Sensing, The University of Adelaide, Adelaide, South Australia, Australia melanie.mcdowall@adelaide.edu.au.
authors.forename: Melanie L
authors.initials: ML
authors.lastname: Sutton-McDowall
authors.affiliation: Robinson Research Institute, School of Medicine, The University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Linda L Y
authors.initials: LL
authors.lastname: Wu
authors.affiliation: Australian Research Council Centre of Excellence for Nanoscale BioPhotonics Institute of Photonics and Advanced Sensing, The University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Malcolm
authors.initials: M
authors.lastname: Purdey
authors.affiliation: Australian Research Council Centre of Excellence for Nanoscale BioPhotonics Institute of Photonics and Advanced Sensing, The University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Abell
authors.affiliation: Australian Research Council Centre of Excellence for Nanoscale BioPhotonics MQ BioFocus Research Centre, Macquarie University, North Ryde, New South Wales, Australia.
authors.forename: Ewa M
authors.initials: EM
authors.lastname: Goldys
authors.affiliation: Department of Veterinary Science, The University of Melbourne, Werribee, Victoria, Australia.
authors.forename: Keith L
authors.initials: KL
authors.lastname: MacMillan
authors.affiliation: Australian Research Council Centre of Excellence for Nanoscale BioPhotonics Robinson Research Institute, School of Medicine, The University of Adelaide, Adelaide, South Australia, Australia Institute of Photonics and Advanced Sensing, The University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Jeremy G
authors.initials: JG
authors.lastname: Thompson
authors.affiliation: Robinson Research Institute, School of Medicine, The University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Robker
mesh_terms: D051701:Activating Transcription Factor 4 / Q000378:metabolism; D051702:Activating Transcription Factor 6 / Q000378:metabolism; D000818:Animals; D002417:Cattle; D002934:Cinnamates / Q000494:pharmacology; D054885:Cumulus Cells / Q000187:drug effects* / Q000378:metabolism*; D046149:Embryo Culture Techniques; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology*; D005260:Female; D005182:Flavin-Adenine Dinucleotide / Q000378:metabolism; D018628:Gene Dosage; D005947:Glucose / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D009865:Oocytes / Q000187:drug effects* / Q000378:metabolism*; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D051702:Activating Transcription Factor 6; D002934:Cinnamates; D000091342:Endoplasmic Reticulum Chaperone BiP; D005230:Fatty Acids, Nonesterified; D006360:Heat-Shock Proteins; C496827:salubrinal; D051701:Activating Transcription Factor 4; D005182:Flavin-Adenine Dinucleotide; D019344:Lactic Acid; D013890:Thiourea; D005947:Glucose
keywords: cattle; cumulus oocyte complex; endoplasmic reticulum stress; lipids; nonesterified fatty acids