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Hypoxic in vitro culture reduces histone lactylation and impairs pre-implantation embryonic development in mice
BACKGROUND: Dynamic changes of histone posttranslational modifications are important contexts of epigenetic reprograming after fertilization in pre-implantation embryos. Recently, lactylation has been reported as a novel epigenetic modification that regulates various cellular processes, but its role...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8691063/ https://www.ncbi.nlm.nih.gov/pubmed/34930415 http://dx.doi.org/10.1186/s13072-021-00431-6 |
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author | Yang, Wanting Wang, Peijun Cao, Pengbo Wang, Shuang Yang, Yuxiao Su, Huimin Nashun, Buhe |
author_facet | Yang, Wanting Wang, Peijun Cao, Pengbo Wang, Shuang Yang, Yuxiao Su, Huimin Nashun, Buhe |
author_sort | Yang, Wanting |
collection | PubMed |
description | BACKGROUND: Dynamic changes of histone posttranslational modifications are important contexts of epigenetic reprograming after fertilization in pre-implantation embryos. Recently, lactylation has been reported as a novel epigenetic modification that regulates various cellular processes, but its role during early embryogenesis has not been elucidated. RESULTS: We examined nuclear accumulation of H3K23la, H3K18la and pan histone lactylation in mouse oocytes and pre-implantation embryos by immunofluorescence with specific antibodies. All of the three modifications were abundant in GV stage oocytes, and both H3K23la and pan histone lactylation could be detected on the condensed chromosomes of the MII oocytes, while H3K18la were not detected. After fertilization, the nuclear staining of H3K23la, H3K18la and pan histone lactylation was faint in zygotes but homogeneously stained both of the parental pronuclei. The signal remained weak in the early cleavage stage embryos and increased remarkably in the blastocyst stage embryos. Comparison of the embryos cultured in four different conditions with varying concentrations of oxygen found that H3K23la, H3K18la and pan histone lactylation showed similar and comparable staining pattern in embryos cultured in atmospheric oxygen concentration (20% O(2)), gradient oxygen concentration (5% O(2) to 2% O(2)) and embryos obtained from in vivo, but the modifications were greatly reduced in embryos cultured in hypoxic condition (2% O(2)). In contrast, nuclear accumulation of H3K18ac or H3K23ac was not significantly affected under hypoxic condition. Moreover, the developmental rate of in vitro cultured embryo was significantly reduced by low oxygen concentration and small molecule inhibition of LDHA activity led to decreased lactate production, as well as reduced histone lactylation and compromised developmental rate. CONCLUSIONS: We provided for the first time the dynamic landscape of H3K23la, H3K18la and pan histone lactylation in oocytes and pre-implantation embryos in mice. Our data suggested that histone lactylation is subjected to oxygen concentration in the culture environment and hypoxic in vitro culture reduces histone lactylation, which in turn compromises developmental potential of pre-implantation embryos in mice. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13072-021-00431-6. |
format | Online Article Text |
id | pubmed-8691063 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-86910632021-12-23 Hypoxic in vitro culture reduces histone lactylation and impairs pre-implantation embryonic development in mice Yang, Wanting Wang, Peijun Cao, Pengbo Wang, Shuang Yang, Yuxiao Su, Huimin Nashun, Buhe Epigenetics Chromatin Research BACKGROUND: Dynamic changes of histone posttranslational modifications are important contexts of epigenetic reprograming after fertilization in pre-implantation embryos. Recently, lactylation has been reported as a novel epigenetic modification that regulates various cellular processes, but its role during early embryogenesis has not been elucidated. RESULTS: We examined nuclear accumulation of H3K23la, H3K18la and pan histone lactylation in mouse oocytes and pre-implantation embryos by immunofluorescence with specific antibodies. All of the three modifications were abundant in GV stage oocytes, and both H3K23la and pan histone lactylation could be detected on the condensed chromosomes of the MII oocytes, while H3K18la were not detected. After fertilization, the nuclear staining of H3K23la, H3K18la and pan histone lactylation was faint in zygotes but homogeneously stained both of the parental pronuclei. The signal remained weak in the early cleavage stage embryos and increased remarkably in the blastocyst stage embryos. Comparison of the embryos cultured in four different conditions with varying concentrations of oxygen found that H3K23la, H3K18la and pan histone lactylation showed similar and comparable staining pattern in embryos cultured in atmospheric oxygen concentration (20% O(2)), gradient oxygen concentration (5% O(2) to 2% O(2)) and embryos obtained from in vivo, but the modifications were greatly reduced in embryos cultured in hypoxic condition (2% O(2)). In contrast, nuclear accumulation of H3K18ac or H3K23ac was not significantly affected under hypoxic condition. Moreover, the developmental rate of in vitro cultured embryo was significantly reduced by low oxygen concentration and small molecule inhibition of LDHA activity led to decreased lactate production, as well as reduced histone lactylation and compromised developmental rate. CONCLUSIONS: We provided for the first time the dynamic landscape of H3K23la, H3K18la and pan histone lactylation in oocytes and pre-implantation embryos in mice. Our data suggested that histone lactylation is subjected to oxygen concentration in the culture environment and hypoxic in vitro culture reduces histone lactylation, which in turn compromises developmental potential of pre-implantation embryos in mice. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13072-021-00431-6. BioMed Central 2021-12-21 /pmc/articles/PMC8691063/ /pubmed/34930415 http://dx.doi.org/10.1186/s13072-021-00431-6 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Yang, Wanting Wang, Peijun Cao, Pengbo Wang, Shuang Yang, Yuxiao Su, Huimin Nashun, Buhe Hypoxic in vitro culture reduces histone lactylation and impairs pre-implantation embryonic development in mice |
title | Hypoxic in vitro culture reduces histone lactylation and impairs pre-implantation embryonic development in mice |
title_full | Hypoxic in vitro culture reduces histone lactylation and impairs pre-implantation embryonic development in mice |
title_fullStr | Hypoxic in vitro culture reduces histone lactylation and impairs pre-implantation embryonic development in mice |
title_full_unstemmed | Hypoxic in vitro culture reduces histone lactylation and impairs pre-implantation embryonic development in mice |
title_short | Hypoxic in vitro culture reduces histone lactylation and impairs pre-implantation embryonic development in mice |
title_sort | hypoxic in vitro culture reduces histone lactylation and impairs pre-implantation embryonic development in mice |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8691063/ https://www.ncbi.nlm.nih.gov/pubmed/34930415 http://dx.doi.org/10.1186/s13072-021-00431-6 |
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