Cargando…

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

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 s...

Descripción completa

Detalles Bibliográficos
Autores principales: Sidrat, Tabinda, Khan, Abdul Aziz, Joo, Myeon-Don, Wei, Yiran, Lee, Kyeong-Lim, Xu, Lianguang, Kong, Il-Keun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7593913/
https://www.ncbi.nlm.nih.gov/pubmed/33066562
http://dx.doi.org/10.3390/ijms21207589
_version_ 1783601502536859648
author Sidrat, Tabinda
Khan, Abdul Aziz
Joo, Myeon-Don
Wei, Yiran
Lee, Kyeong-Lim
Xu, Lianguang
Kong, Il-Keun
author_facet Sidrat, Tabinda
Khan, Abdul Aziz
Joo, Myeon-Don
Wei, Yiran
Lee, Kyeong-Lim
Xu, Lianguang
Kong, Il-Keun
author_sort Sidrat, Tabinda
collection PubMed
description 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.
format Online
Article
Text
id pubmed-7593913
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-75939132020-10-30 Bovine Oviduct Epithelial Cell-Derived Culture Media and Exosomes Improve Mitochondrial Health by Restoring Metabolic Flux during Pre-Implantation Development Sidrat, Tabinda Khan, Abdul Aziz Joo, Myeon-Don Wei, Yiran Lee, Kyeong-Lim Xu, Lianguang Kong, Il-Keun Int J Mol Sci Article 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. MDPI 2020-10-14 /pmc/articles/PMC7593913/ /pubmed/33066562 http://dx.doi.org/10.3390/ijms21207589 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sidrat, Tabinda
Khan, Abdul Aziz
Joo, Myeon-Don
Wei, Yiran
Lee, Kyeong-Lim
Xu, Lianguang
Kong, Il-Keun
Bovine Oviduct Epithelial Cell-Derived Culture Media and Exosomes Improve Mitochondrial Health by Restoring Metabolic Flux during Pre-Implantation Development
title Bovine Oviduct Epithelial Cell-Derived Culture Media and Exosomes Improve Mitochondrial Health by Restoring Metabolic Flux during Pre-Implantation Development
title_full Bovine Oviduct Epithelial Cell-Derived Culture Media and Exosomes Improve Mitochondrial Health by Restoring Metabolic Flux during Pre-Implantation Development
title_fullStr Bovine Oviduct Epithelial Cell-Derived Culture Media and Exosomes Improve Mitochondrial Health by Restoring Metabolic Flux during Pre-Implantation Development
title_full_unstemmed Bovine Oviduct Epithelial Cell-Derived Culture Media and Exosomes Improve Mitochondrial Health by Restoring Metabolic Flux during Pre-Implantation Development
title_short Bovine Oviduct Epithelial Cell-Derived Culture Media and Exosomes Improve Mitochondrial Health by Restoring Metabolic Flux during Pre-Implantation Development
title_sort bovine oviduct epithelial cell-derived culture media and exosomes improve mitochondrial health by restoring metabolic flux during pre-implantation development
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7593913/
https://www.ncbi.nlm.nih.gov/pubmed/33066562
http://dx.doi.org/10.3390/ijms21207589
work_keys_str_mv AT sidrattabinda bovineoviductepithelialcellderivedculturemediaandexosomesimprovemitochondrialhealthbyrestoringmetabolicfluxduringpreimplantationdevelopment
AT khanabdulaziz bovineoviductepithelialcellderivedculturemediaandexosomesimprovemitochondrialhealthbyrestoringmetabolicfluxduringpreimplantationdevelopment
AT joomyeondon bovineoviductepithelialcellderivedculturemediaandexosomesimprovemitochondrialhealthbyrestoringmetabolicfluxduringpreimplantationdevelopment
AT weiyiran bovineoviductepithelialcellderivedculturemediaandexosomesimprovemitochondrialhealthbyrestoringmetabolicfluxduringpreimplantationdevelopment
AT leekyeonglim bovineoviductepithelialcellderivedculturemediaandexosomesimprovemitochondrialhealthbyrestoringmetabolicfluxduringpreimplantationdevelopment
AT xulianguang bovineoviductepithelialcellderivedculturemediaandexosomesimprovemitochondrialhealthbyrestoringmetabolicfluxduringpreimplantationdevelopment
AT kongilkeun bovineoviductepithelialcellderivedculturemediaandexosomesimprovemitochondrialhealthbyrestoringmetabolicfluxduringpreimplantationdevelopment