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ORIGINAL RESEARCH article
Front. Cell Dev. Biol.
Sec. Embryonic Development
Volume 12 - 2024 |
doi: 10.3389/fcell.2024.1507102
Regulation of α-Ketoglutarate Levels by Myc Affects Metabolism and Demethylation in Porcine Early Embryos
Provisionally accepted
Ran Ding
1*
Yongfeng Zhou
1*
Qi Zhang
1*
Xiangjie Kong
1*
Qi Li
1*
Sheng Zhang
1*
Yibing Chen
2*
Xinglan An
1*
Ziyi Li
1*- 1 First Affiliated Hospital of Jilin University, Changchun, China
- 2 Jilin Hospital, Obstetrics and Gynecology Hospital Affiliated to Zhejiang University School of Medicine, ChangChun, China
The Myc family is essential for cell proliferation, differentiation, and metabolism, particularly in embryonic development and stem cell functions. However, the specific role of Myc in porcine early embryonic development is not fully understood. This study observed high Myc expression during the four-cell stage of porcine embryos. Inhibition of Myc using 10058-F4 impaired embryonic development, disrupted energy metabolism, and increased DNA methylation. Mechanistically, these effects were dependent on α-KG, a TCA cycle intermediate and cofactor for TET demethylation enzymes. Sequencing analysis of four-cell embryos post-Myc inhibition revealed downregulation of key metabolic enzymes related to α-KG, such as CS, IDH2, leading to reduced α-KG levels.Supplementation with α-Ketoglutarate(α-KG) mitigated the negative effects of Myc inhibition, including lower blastocyst rates, decreased ATP levels, and increased 5mC levels. In conclusion, Myc regulates the expression of key metabolic enzymes during the four-cell stage, influencing early embryonic metabolism and epigenetic reprogramming(Figure 1).
Keywords: MYC, α-KG, Metabolism, Demethylation, Early embryos, pigs
Received: 07 Oct 2024; Accepted: 04 Nov 2024.
Copyright: © 2024 Ding, Zhou, Zhang, Kong, Li, Zhang, Chen, An and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Ran Ding, First Affiliated Hospital of Jilin University, Changchun, China
Yongfeng Zhou, First Affiliated Hospital of Jilin University, Changchun, China
Qi Zhang, First Affiliated Hospital of Jilin University, Changchun, China
Xiangjie Kong, First Affiliated Hospital of Jilin University, Changchun, China
Qi Li, First Affiliated Hospital of Jilin University, Changchun, China
Sheng Zhang, First Affiliated Hospital of Jilin University, Changchun, China
Yibing Chen, Jilin Hospital, Obstetrics and Gynecology Hospital Affiliated to Zhejiang University School of Medicine, ChangChun, China
Xinglan An, First Affiliated Hospital of Jilin University, Changchun, China
Ziyi Li, First Affiliated Hospital of Jilin University, Changchun, China
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