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Article

Bovine Oviduct Epithelial Cell-Derived Culture Media and Exosomes Improve Mitochondrial Health by Restoring Metabolic Flux during Pre-Implantation Development

1
Department of Animal Science, Division of Applied Life Science (BK21 Four), Gyeongsang National University, Jinju 52828, Korea
2
Center for Discovery and Innovation, Hackensack University Medical Center, Nutley, NJ 07110, USA
3
The King Kong Corp. Ltd., Gyeongsang National University, Jinju 52828, Korea
4
Institute of Agriculture and Life Science, Gyeongsang National University, Jinju 52828, Korea
*
Author to whom correspondence should be addressed.
Joint first authors.
Int. J. Mol. Sci. 2020, 21(20), 7589; https://doi.org/10.3390/ijms21207589
Received: 28 September 2020 / Revised: 9 October 2020 / Accepted: 12 October 2020 / Published: 14 October 2020
(This article belongs to the Section Molecular Endocrinology and Metabolism)
Oviduct flushing is enriched by a wide variety of nutrients that guide the 3–4 days journey of pre-implantation embryo through the oviduct as it develops into a competent blastocyst (BL). However, little is known about the specific requirement and role of these nutrients that orchestrate the early stages of embryonic development. In this study, we aimed to characterize the effect of in vitro-derived bovine oviduct epithelial cell (BOECs) secretion that mimics the in vivo oviduct micro-fluid like environment, which allows successful embryonic development. In this study, the addition of an in vitro derived BOECs-condition media (CM) and its isolated exosomes (Exo) significantly enhances the quality and development of BL, while the hatching ability of BLs was found to be high (48.8%) in the BOECs-Exo supplemented group. Surprisingly, BOECs-Exo have a dynamic effect on modulating the embryonic metabolism by restoring the pyruvate flux into TCA-cycle. Our analysis reveals that Exo treatment significantly upregulates the pyruvate dehydrogenase (PDH) and glutamate dehydrogenase (GLUD1) expression, required for metabolic fine-tuning of the TCA-cycle in the developing embryos. Exo treatment increases the influx into TCA-cycle by strongly suppressing the PDH and GLUD1 upstream inhibitors, i.e., PDK4 and SIRT4. Improvement of TCA-cycle function was further accompanied by higher metabolic activity of mitochondria in BOECs-CM and Exo in vitro embryos. Our study uncovered, for the first time, the possible mechanism of BOECs-derived secretion in re-establishing the TCA-cycle flux by the utilization of available nutrients and highlighted the importance of pyruvate in supporting bovine in vitro embryonic development. View Full-Text
Keywords: oviduct epithelial cells; exosomes; TCA-cycle; metabolism; bovine embryo oviduct epithelial cells; exosomes; TCA-cycle; metabolism; bovine embryo
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MDPI and ACS Style

Sidrat, T.; Khan, A.A.; Joo, M.-D.; Wei, Y.; Lee, K.-L.; Xu, L.; Kong, I.-K. Bovine Oviduct Epithelial Cell-Derived Culture Media and Exosomes Improve Mitochondrial Health by Restoring Metabolic Flux during Pre-Implantation Development. Int. J. Mol. Sci. 2020, 21, 7589. https://doi.org/10.3390/ijms21207589

AMA Style

Sidrat T, Khan AA, Joo M-D, Wei Y, Lee K-L, Xu L, Kong I-K. Bovine Oviduct Epithelial Cell-Derived Culture Media and Exosomes Improve Mitochondrial Health by Restoring Metabolic Flux during Pre-Implantation Development. International Journal of Molecular Sciences. 2020; 21(20):7589. https://doi.org/10.3390/ijms21207589

Chicago/Turabian Style

Sidrat, Tabinda, Abdul A. Khan, Myeon-Don Joo, Yiran Wei, Kyeong-Lim Lee, Lianguang Xu, and Il-Keun Kong. 2020. "Bovine Oviduct Epithelial Cell-Derived Culture Media and Exosomes Improve Mitochondrial Health by Restoring Metabolic Flux during Pre-Implantation Development" International Journal of Molecular Sciences 21, no. 20: 7589. https://doi.org/10.3390/ijms21207589

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