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Progesterone Activates the Histone Lactylation-Hif1α-glycolysis Feedback Loop to Promote Decidualization.
Zhao, Wei; Wang, Yue; Liu, Juan; Yang, Qianying; Zhang, Shuai; Hu, Xiao; Shi, Zhicheng; Zhang, Zhenni; Tian, Jianhui; Chu, Dapeng; An, Lei.
Afiliação
  • Zhao W; State Key Laboratory of Animal Biotech Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture and Rural Affairs, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing 100019
  • Wang Y; State Key Laboratory of Animal Biotech Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture and Rural Affairs, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing 100019
  • Liu J; State Key Laboratory of Animal Biotech Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture and Rural Affairs, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing 100019
  • Yang Q; State Key Laboratory of Animal Biotech Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture and Rural Affairs, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing 100019
  • Zhang S; State Key Laboratory of Animal Biotech Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture and Rural Affairs, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing 100019
  • Hu X; State Key Laboratory of Animal Biotech Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture and Rural Affairs, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing 100019
  • Shi Z; State Key Laboratory of Animal Biotech Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture and Rural Affairs, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing 100019
  • Zhang Z; State Key Laboratory of Animal Biotech Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture and Rural Affairs, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing 100019
  • Tian J; State Key Laboratory of Animal Biotech Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture and Rural Affairs, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing 100019
  • Chu D; Medical Center for Human Reproduction, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, P.R. China.
  • An L; State Key Laboratory of Animal Biotech Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture and Rural Affairs, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing 100019
Endocrinology ; 165(1)2023 Nov 20.
Article em En | MEDLINE | ID: mdl-37950883
ABSTRACT
Decidualization is a progesterone-dependent cellular differentiation process that is essential for establishing pregnancy. Robust activation of glycolysis and lactate synthesis during decidualization is remarkable, but their developmental functions remain largely unknown. Herein, we identify that endometrial lactate production plays a critical role in establishing local histone lactylation, a newly identified histone modification, and is important for ensuring normal decidualization. Enhanced endometrial glycolysis is the hallmark metabolic change and is tightly coupled with H4K12la during decidualization. Inhibition of histone lactylation impaired decidualization, in either physiological conception or in vivo and in vitro induced decidualization models. Mechanistic study based on CUT&Tag and ATAC-seq revealed that a transcriptional factor hypoxia-inducible factor 1 α (Hif1α) is the critical regulatory target of H4K12la, and in turn forms an H4K12la-Hif1α-glycolysis feedback loop to drive decidualization. Moreover, we demonstrate that the loop is directly activated by progesterone during decidualization. Our study not only advances the current knowledge of the role of lactate in regulating uterine function, but also establishes a novel functional link among the major endocrine factors, endometrial metabolic change, and epigenetic modification during endometrial remodeling. These findings present valuable clues to develop clinical intervention strategies to improve pregnancy outcomes following both natural conception and assisted reproduction.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Progesterona / Histonas Limite: Female / Humans / Pregnancy Idioma: En Revista: Endocrinology Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Progesterona / Histonas Limite: Female / Humans / Pregnancy Idioma: En Revista: Endocrinology Ano de publicação: 2023 Tipo de documento: Article
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