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α-Ketoglutarate enhances epigenetic remodeling and developmental competence in porcine SCNT embryos.

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Τίτλος: α-Ketoglutarate enhances epigenetic remodeling and developmental competence in porcine SCNT embryos.
Συγγραφείς: Zhao B; College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China.; Key Laboratory of Animal Biotechnology, Ministry of Agriculture and Rural Affairs, Northwest A&F University, Yangling, Shaanxi, PR China., Wang J; College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China.; Key Laboratory of Animal Biotechnology, Ministry of Agriculture and Rural Affairs, Northwest A&F University, Yangling, Shaanxi, PR China., Xu Z; College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China.; Key Laboratory of Animal Biotechnology, Ministry of Agriculture and Rural Affairs, Northwest A&F University, Yangling, Shaanxi, PR China., Guo X; College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China.; Key Laboratory of Animal Biotechnology, Ministry of Agriculture and Rural Affairs, Northwest A&F University, Yangling, Shaanxi, PR China., Wang S; College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China.; Key Laboratory of Animal Biotechnology, Ministry of Agriculture and Rural Affairs, Northwest A&F University, Yangling, Shaanxi, PR China., Yin Z; College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China.; Key Laboratory of Animal Biotechnology, Ministry of Agriculture and Rural Affairs, Northwest A&F University, Yangling, Shaanxi, PR China., Li Y; College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China.; Key Laboratory of Animal Biotechnology, Ministry of Agriculture and Rural Affairs, Northwest A&F University, Yangling, Shaanxi, PR China., Lv M; College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China.; Key Laboratory of Animal Biotechnology, Ministry of Agriculture and Rural Affairs, Northwest A&F University, Yangling, Shaanxi, PR China., Liu J; College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China.; Key Laboratory of Animal Biotechnology, Ministry of Agriculture and Rural Affairs, Northwest A&F University, Yangling, Shaanxi, PR China., Li H; College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China.; Key Laboratory of Animal Biotechnology, Ministry of Agriculture and Rural Affairs, Northwest A&F University, Yangling, Shaanxi, PR China., Qing S; College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China.; Key Laboratory of Animal Biotechnology, Ministry of Agriculture and Rural Affairs, Northwest A&F University, Yangling, Shaanxi, PR China., Wang Y; College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China.; Key Laboratory of Animal Biotechnology, Ministry of Agriculture and Rural Affairs, Northwest A&F University, Yangling, Shaanxi, PR China.
Πηγή: Reproduction (Cambridge, England) [Reproduction] 2026 Sep 03; Vol. 172 (3).
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Published for the Society for Reproduction and Fertility by BioScientifica Country of Publication: England NLM ID: 100966036 Publication Model: Print Cited Medium: Internet ISSN: 1741-7899 (Electronic) Linking ISSN: 14701626 NLM ISO Abbreviation: Reproduction Subsets: MEDLINE
Imprint Name(s): Publication: <2004->: Bristol, UK : Published for the Society for Reproduction and Fertility by BioScientifica
Original Publication: Cambridge, UK : Journals of Reproduction and Fertility, Ltd. c2001-
Ιατρικοί όροι (MeSH): Nuclear Transfer Techniques*/veterinary , Epigenesis, Genetic*/drug effects , Ketoglutaric Acids*/pharmacology , Embryonic Development*/drug effects , Cellular Reprogramming*/drug effects , Embryo, Mammalian*/drug effects , Embryo, Mammalian*/metabolism, Gene Expression Regulation, Developmental/drug effects ; Blastocyst/drug effects ; Blastocyst/metabolism ; Blastocyst/cytology ; Zygote/drug effects ; Zygote/metabolism ; Animals ; Swine ; Female
Περίληψη: In Brief: Zygotic genome activation failure contributes to the low developmental efficiency of porcine somatic cell nuclear transfer (SCNT) embryos. We show that α-ketoglutarate improves transcriptional activation, epigenetic remodeling, and embryo development in SCNT embryos, supporting its potential use for improving nuclear reprogramming efficiency.
Abstract: Abstract: Incomplete zygotic genome activation (ZGA) is a major barrier limiting the developmental competence of somatic cell nuclear transfer (SCNT) embryos in pigs. α-Ketoglutarate (α-KG), a key metabolic intermediate and cofactor for α-KG-dependent dioxygenases, has been implicated in epigenetic remodeling during early embryogenesis. In this study, we investigated whether α-KG supplementation could improve developmental potential and ZGA-associated events in porcine SCNT embryos. Treatment with α-KG improved cleavage progression, increased blastocyst formation rates, increased total blastocyst cell number and inner cell mass cell number, and reduced apoptosis and DNA damage. In addition, α-KG improved microtubule organization and actin distribution during early cleavage stages, contributing to more coordinated cell division. Mechanistically, α-KG increased global 5-hydroxymethylcytosine (5hmC) levels and elevated the abundance of activating histone marks, including H3K4me3 and H3K27ac. Expression of several ZGA-associated genes, including DUXA, ZSCAN4, EIF1A, and KLF17, was significantly increased following α-KG supplementation, accompanied by enhanced nascent RNA synthesis. Notably, inhibition of TET enzymes with Bobcat339 attenuated the effects of α-KG on 5hmC accumulation, transcriptional activity, and embryo development. Collectively, these findings indicate that α-KG improves developmental competence and is associated with enhanced epigenetic remodeling in porcine SCNT embryos, at least in part through TET-associated pathways, providing a potential strategy for improving nuclear reprogramming efficiency in animal cloning.
(© The Author(s) 2026. Published by Oxford University Press on behalf of the Society for Reproduction and Fertility. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
Grant Information: 2021YFD1200303 National Key R&D Program; 2024BBF01005 Ningxia Hui Autonomous Region key R&D; 2024ZY-JCYJ-02-19 Shanxi Province Natural Science Foundation; 2024NC2-GJHX-13 Key R&D Program of Shaanxi Province
Contributed Indexing: Keywords: TET enzymes; epigenetic reprogramming; porcine embryo; somatic cell nuclear transfer; zygotic genome activation; α-ketoglutarate
Substance Nomenclature: 0 (Ketoglutaric Acids)
Entry Date(s): Date Created: 20260826 Date Completed: 20260918 Latest Revision: 20260918
Update Code: 20260919
DOI: 10.1093/reprod/xaag103
PMID: 42644820
Βάση Δεδομένων: MEDLINE
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  Data: α-Ketoglutarate enhances epigenetic remodeling and developmental competence in porcine SCNT embryos.
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  Data: &lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Zhao+B%22&quot;&gt;Zhao B&lt;/searchLink&gt;; College of Veterinary Medicine, Northwest A&amp;F University, Yangling, Shaanxi, China.; Key Laboratory of Animal Biotechnology, Ministry of Agriculture and Rural Affairs, Northwest A&amp;F University, Yangling, Shaanxi, PR China.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Wang+J%22&quot;&gt;Wang J&lt;/searchLink&gt;; College of Veterinary Medicine, Northwest A&amp;F University, Yangling, Shaanxi, China.; Key Laboratory of Animal Biotechnology, Ministry of Agriculture and Rural Affairs, Northwest A&amp;F University, Yangling, Shaanxi, PR China.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Xu+Z%22&quot;&gt;Xu Z&lt;/searchLink&gt;; College of Veterinary Medicine, Northwest A&amp;F University, Yangling, Shaanxi, China.; Key Laboratory of Animal Biotechnology, Ministry of Agriculture and Rural Affairs, Northwest A&amp;F University, Yangling, Shaanxi, PR China.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Guo+X%22&quot;&gt;Guo X&lt;/searchLink&gt;; College of Veterinary Medicine, Northwest A&amp;F University, Yangling, Shaanxi, China.; Key Laboratory of Animal Biotechnology, Ministry of Agriculture and Rural Affairs, Northwest A&amp;F University, Yangling, Shaanxi, PR China.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Wang+S%22&quot;&gt;Wang S&lt;/searchLink&gt;; College of Veterinary Medicine, Northwest A&amp;F University, Yangling, Shaanxi, China.; Key Laboratory of Animal Biotechnology, Ministry of Agriculture and Rural Affairs, Northwest A&amp;F University, Yangling, Shaanxi, PR China.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Yin+Z%22&quot;&gt;Yin Z&lt;/searchLink&gt;; College of Veterinary Medicine, Northwest A&amp;F University, Yangling, Shaanxi, China.; Key Laboratory of Animal Biotechnology, Ministry of Agriculture and Rural Affairs, Northwest A&amp;F University, Yangling, Shaanxi, PR China.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Li+Y%22&quot;&gt;Li Y&lt;/searchLink&gt;; College of Veterinary Medicine, Northwest A&amp;F University, Yangling, Shaanxi, China.; Key Laboratory of Animal Biotechnology, Ministry of Agriculture and Rural Affairs, Northwest A&amp;F University, Yangling, Shaanxi, PR China.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Lv+M%22&quot;&gt;Lv M&lt;/searchLink&gt;; College of Veterinary Medicine, Northwest A&amp;F University, Yangling, Shaanxi, China.; Key Laboratory of Animal Biotechnology, Ministry of Agriculture and Rural Affairs, Northwest A&amp;F University, Yangling, Shaanxi, PR China.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Liu+J%22&quot;&gt;Liu J&lt;/searchLink&gt;; College of Veterinary Medicine, Northwest A&amp;F University, Yangling, Shaanxi, China.; Key Laboratory of Animal Biotechnology, Ministry of Agriculture and Rural Affairs, Northwest A&amp;F University, Yangling, Shaanxi, PR China.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Li+H%22&quot;&gt;Li H&lt;/searchLink&gt;; College of Veterinary Medicine, Northwest A&amp;F University, Yangling, Shaanxi, China.; Key Laboratory of Animal Biotechnology, Ministry of Agriculture and Rural Affairs, Northwest A&amp;F University, Yangling, Shaanxi, PR China.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Qing+S%22&quot;&gt;Qing S&lt;/searchLink&gt;; College of Veterinary Medicine, Northwest A&amp;F University, Yangling, Shaanxi, China.; Key Laboratory of Animal Biotechnology, Ministry of Agriculture and Rural Affairs, Northwest A&amp;F University, Yangling, Shaanxi, PR China.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Wang+Y%22&quot;&gt;Wang Y&lt;/searchLink&gt;; College of Veterinary Medicine, Northwest A&amp;F University, Yangling, Shaanxi, China.; Key Laboratory of Animal Biotechnology, Ministry of Agriculture and Rural Affairs, Northwest A&amp;F University, Yangling, Shaanxi, PR China.
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– Name: Abstract
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  Data: In Brief: Zygotic genome activation failure contributes to the low developmental efficiency of porcine somatic cell nuclear transfer (SCNT) embryos. We show that α-ketoglutarate improves transcriptional activation, epigenetic remodeling, and embryo development in SCNT embryos, supporting its potential use for improving nuclear reprogramming efficiency.&lt;br /&gt;Abstract: Abstract: Incomplete zygotic genome activation (ZGA) is a major barrier limiting the developmental competence of somatic cell nuclear transfer (SCNT) embryos in pigs. α-Ketoglutarate (α-KG), a key metabolic intermediate and cofactor for α-KG-dependent dioxygenases, has been implicated in epigenetic remodeling during early embryogenesis. In this study, we investigated whether α-KG supplementation could improve developmental potential and ZGA-associated events in porcine SCNT embryos. Treatment with α-KG improved cleavage progression, increased blastocyst formation rates, increased total blastocyst cell number and inner cell mass cell number, and reduced apoptosis and DNA damage. In addition, α-KG improved microtubule organization and actin distribution during early cleavage stages, contributing to more coordinated cell division. Mechanistically, α-KG increased global 5-hydroxymethylcytosine (5hmC) levels and elevated the abundance of activating histone marks, including H3K4me3 and H3K27ac. Expression of several ZGA-associated genes, including DUXA, ZSCAN4, EIF1A, and KLF17, was significantly increased following α-KG supplementation, accompanied by enhanced nascent RNA synthesis. Notably, inhibition of TET enzymes with Bobcat339 attenuated the effects of α-KG on 5hmC accumulation, transcriptional activity, and embryo development. Collectively, these findings indicate that α-KG improves developmental competence and is associated with enhanced epigenetic remodeling in porcine SCNT embryos, at least in part through TET-associated pathways, providing a potential strategy for improving nuclear reprogramming efficiency in animal cloning.&lt;br /&gt; (&#169; The Author(s) 2026. Published by Oxford University Press on behalf of the Society for Reproduction and Fertility. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
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  Data: 2021YFD1200303 National Key R&amp;D Program; 2024BBF01005 Ningxia Hui Autonomous Region key R&amp;D; 2024ZY-JCYJ-02-19 Shanxi Province Natural Science Foundation; 2024NC2-GJHX-13 Key R&amp;D Program of Shaanxi Province
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  Data: &lt;i&gt;Keywords: &lt;/i&gt;TET enzymes; epigenetic reprogramming; porcine embryo; somatic cell nuclear transfer; zygotic genome activation; α-ketoglutarate
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        Type: general
      – SubjectFull: Blastocyst drug effects
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