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Peer-reviewedCC BY 4.0Biomolecules

Role of Hypoxia-Inducible Factor-1 Alpha in Endometrial Decidualization

  • Defan Wang1
  • Zhenghong Zhang2
  • Renfeng Xu3
  • Zhengchao Wang2
  1. 1Fujian Provincial Key Laboratory of Reproductive Health Research, School of Medicine, Xiamen University, Xiamen 361102, China
  2. 2Provincial Key Laboratory for Developmental Biology and Neurosciences, College of Life Sciences, Fujian Normal University, Fuzhou 350007, China
  3. 3Fujian Key Laboratory of Integrative Medicine on Geriatrics, College of Integrative Medicine, Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China
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Abstract

Endometrial decidualization is a hormonally programmed differentiation and tissue-remodeling process that prepares the endometrium for embryo implantation and supports early pregnancy. It involves coordinated changes in endometrial stromal cells, the extracellular matrix, vascular function, metabolism, and local immune composition. Hypoxia-inducible factor-1α (HIF-1α) is an oxygen-sensitive transcription factor that responds to changes in tissue oxygenation and metabolic state. Evidence from endometrial stromal-cell models and reproductive tissues suggests that HIF-1α may participate in decidual cell differentiation, metabolic adaptation, angiogenic signaling, and immune regulation. However, the strength of evidence differs substantially among these processes, and findings from trophoblasts, placenta, immune cells, or non-reproductive tissues cannot automatically be interpreted as direct evidence for decidual stromal-cell mechanisms. This review summarizes current evidence for HIF-1α in endometrial decidualization, distinguishes direct endometrial findings from mechanistic extrapolation, and considers the interaction of HIF-1α with metabolic, vascular, immune, and epigenetic pathways. Overall, HIF-1α is best considered a context-dependent component of the decidualization network rather than an independent master regulator. Defining its cell-specific and temporal functions, including its relationship with HIF-2α, will be important for determining whether HIF-directed interventions can be developed without disrupting physiological reproductive adaptation.

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Cite

BibTeXRIS
BibTeX
@article{wang2026role,
  title = {{Role of Hypoxia-Inducible Factor-1 Alpha in Endometrial Decidualization}},
  author = {Defan Wang and Zhenghong Zhang and Renfeng Xu and Zhengchao Wang},
  journal = {Biomolecules},
  year = {2026},
  month = oct,
  doi = {10.3390/biom16101483},
  url = {https://www.mdpi.com/2218-273X/16/10/1483},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Role of Hypoxia-Inducible Factor-1 Alpha in Endometrial Decidualization
AU  - Defan Wang
AU  - Zhenghong Zhang
AU  - Renfeng Xu
AU  - Zhengchao Wang
PY  - 2026
DA  - 2026/10/01
JO  - Biomolecules
DO  - 10.3390/biom16101483
UR  - https://www.mdpi.com/2218-273X/16/10/1483
AB  - Endometrial decidualization is a hormonally programmed differentiation and tissue-remodeling process that prepares the endometrium for embryo implantation and supports early pregnancy. It involves coordinated changes in endometrial stromal cells, the extracellular matrix, vascular function, metabolism, and local immune composition. Hypoxia-inducible factor-1α (HIF-1α) is an oxygen-sensitive transcription factor that responds to changes in tissue oxygenation and metabolic state. Evidence from endometrial stromal-cell models and reproductive tissues suggests that HIF-1α may participate in decidual cell differentiation, metabolic adaptation, angiogenic signaling, and immune regulation. However, the strength of evidence differs substantially among these processes, and findings from trophoblasts, placenta, immune cells, or non-reproductive tissues cannot automatically be interpreted as direct evidence for decidual stromal-cell mechanisms. This review summarizes current evidence for HIF-1α in endometrial decidualization, distinguishes direct endometrial findings from mechanistic extrapolation, and considers the interaction of HIF-1α with metabolic, vascular, immune, and epigenetic pathways. Overall, HIF-1α is best considered a context-dependent component of the decidualization network rather than an independent master regulator. Defining its cell-specific and temporal functions, including its relationship with HIF-2α, will be important for determining whether HIF-directed interventions can be developed without disrupting physiological reproductive adaptation.
SN  - 2218-273X
ER  -