β-hydroxybutyrate impairs bovine oocyte maturation via pyruvate dehydrogenase (PDH) associated energy metabolism abnormality

β-羟基丁酸通过丙酮酸脱氢酶(PDH)相关的能量代谢异常损害牛卵母细胞的成熟

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作者:Kai-Yan Zhang, Jing Guo, Cheng-Lin Zhan, Chong-Shan Yuan, Chang-Guo Min, Zhi-Qiang Li, Hong-Yu Liu, Jun Wang, Jing Zhao, Wen-Fa Lu, Xin Ma

Background

Ketosis is one of the most frequent and costly metabolic disorders in high-producing dairy cows, and negatively associated with the health and reproductive performance of bovine. Ketosis is mainly caused by the accumulation of ketone body β-hydroxybutyric acid and its diagnosis is based on β-hydroxybutyrate (βHB) concentration in blood.

Conclusion

Our study showed that βHB in subclinical/clinical concentration had toxic effects on mitochondrial function and PDH activity, which might affect energy metabolism and epigenetic modification of bovine oocytes and embryos.

Methods

In this study, we investigated the effects of βHB on bovine oocyte maturation in the concentration of subclinical (1.2 mM) βHB and clinical (3.6 mM).

Results

The results showed βHB disrupted bovine oocyte maturation and development capacity. Further analysis showed that βHB induced oxidative stress and mitochondrial dysfunction, as indicated by the increased level of reactive oxygen species (ROS), disrupted mitochondrial structure and distribution, and depolarized membrane potential. Furthermore, oxidative stress triggered early apoptosis, as shown by the enhanced levels of Caspase-3 and Annexin-V. Moreover, 3.6 mM βHB induced the disruption of the pyruvate dehydrogenase (PDH) activity, showing with the decrease of the global acetylation modification and the increase of the abnormal spindle rate.

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