Addition of an ER-stress inhibitor overcomes the compromised development of cow COCs matured in vitro with elevated fatty acids — ASN Events
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  3. Addition of an ER-stress inhibitor overcomes the compromised development of cow COCs matured in vitro with elevated fatty acids

Addition of an ER-stress inhibitor overcomes the compromised development of cow COCs matured in vitro with elevated fatty acids (#226)

Melanie L Sutton-McDowall 1 , Rebecca L Robker 1 , Jeremy G Thompson 1
  1. The Robinson Research Institute, School of Paediatrics and Reproductive Health, The University of Adelaide, Adelaide, SA, Australia

The fertility of high performance (high milk yielding) dairy cattle has steadily declined over the past two decades and is a major problem facing productivity within the Australian dairy industry. A 12-month calving interval, where the timing of parturition and peak lactation coincides with peak pasture production, is essential under Australian conditions. However, this requires cows to be in-calf within 90 days post-partum, which coincides with loss of body condition, negative energy balance and mobilisation of fat stores. The resulting imbalance in nutrients, especially accumulation of non-esterified fatty acids (NEFAs) within ovarian follicles, is thought to have a major impact on oocyte quality and partly accounts for compromised fertility. We hypothesise that 1) cumulus oocyte complexes (COCs) exposed to elevated NEFAs have increased lipid accumulation, altered metabolism and poor developmental competence and 2) this can be reversed by treatment with an inhibitor of an endoplasmic reticulum (ER) stress (salubrinal).

Abattoir-derived immature cow COCs were cultured in 1) control (VitroMat + BSA + FSH; 2) NEFA (150μM palmitic acid, 250μM oleic acid, 75μM steric acid); 3) 400nM salubrinal and 4) NEFA + salubrinal. NEFA supplementation significantly increased lipid accumulation within the oocyte and significantly decreased total blastocyst development post-fertilisation (control=49.5±1.2% vs. NEFA=37.9±2.7%; P<0.05). Salubrinal supplementation to NEFA-exposed COCs recovered blastocyst development to levels comparable to the control group and recovered impaired glycolytic activity (glucose and lactate turnover). NEFA supplementation reduced oxidative phosphorylation within oocytes (FAD++ fluorescence); salubrinal supplementation was unable to recover this.

These experiments demonstrate that salubrinal supplementation can reverse the negative impacts on carbohydrate metabolism and embryo development caused by elevated NEFA during oocyte maturation. While further work is required to resolve the imbalance in oxidative phosphorylation, we have identified a potential target pathway to improve dairy cattle fertility.

Funded by the Gardiner Foundation (INN-12-041).

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