Proline-PRODH metabolism promotes placental angiogenesis via the mtROS-STAT3-bFGF/VEGF-A axis

Shuangbo Huang; Deyuan Wu; Zhihui Chen; Chengjun Hu; Kaidi Ma; Jie Peng; Yulong Yin; Chengquan Tan

doi:10.59717/j.xinn-life.2026.100233

The Innovation Life > 2026 Vol. 4 > No. 3 > 100233

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Proline-PRODH metabolism promotes placental angiogenesis via the mtROS-STAT3-bFGF/VEGF-A axis

1.
State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science, South China Agricultural University, Guangzhou 510642, China
2.
College of Animal Science, Fujian Agriculture and Forestry University, Fuzhou 350002, China
3.
Engineering Research Center for Animal Breeding and Sustainable Production, Fujian Agriculture and Forestry University, Fuzhou 350002, China
4.
Tropical Crop Genetic Resource Research Institute, Chinese Academy of Tropical Agricultural Sciences, Haikou 571101, China
5.
College of Animal Science and Technology, Zhongkai University of Agriculture and Engineering, Guangzhou 510225, China
6.
Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha 410125, China

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Corresponding authors: pengjie@zhku.edu.cn (J.P.); yinyulong@isa.ac.cn (Y.Y.); tanchengquan@scau.edu.cn (C.T.)
Received Date: December 04, 2025

Accepted Date: June 26, 2026

Published Online: June 30, 2026

The Innovation Life 4(3), https://doi.org/10.59717/j.xinn-life.2026.100233 | Cite this article

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GRAPHICAL ABSTRACT

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PUBLIC SUMMARY

PUBLIC SUMMARY
1. Dietary proline (Pro) deficiency damages placental angiogenesis and raises low birth weight risk.
  
  Proline regulates placental angiogenesis via mitochondrial reactive oxygen species (mtROS).
  
  mtROS regulates the activation of signal transducer and activator of transcription 3 and angiogenic factors.
  
  Pro dehydrogenase metabolism maintains mtROS homeostasis via sirtuin 1/superoxide dismutase 2 pathways.

ABSTRACT

ABSTRACT

Functional amino acids have been shown to regulate fetal and placental development. However, little is known about the role and mechanism of proline (Pro) in placental angiogenesis. Here, we analyzed amino acid profiles and vascular development in pig placentae at different gestational time points, and found that decreased placental Pro availability was associated with impaired angiogenesis. In a nutrient-restricted mouse model, dietary Pro deficiency reduced placental proline availability, further increased the incidence of low birth weight (LBW), and exacerbated placental vascular defects. Mechanistically, Pro regulates mitochondrial reactive oxygen species (mtROS) homeostasis and subsequently promotes placental angiogenesis through the mediation of phospho-signal transducer and activator of transcription 3 (p-STAT3^Tyr705)-basic fibroblast growth factor (bFGF)/vascular endothelial growth factor A (VEGF-A) pathway. Moreover, Pro-proline dehydrogenase (PRODH) metabolism maintains mtROS homeostasis through glutathione-independent and Sirtuin 1/superoxide dismutase 2-dependent pathways. Collectively, these results demonstrate that dietary Pro plays a crucial role in placental angiogenesis and identify the Pro-PRODH-mtROS- STAT3-bFGF/VEGF-A axis as a potential target for the prevention of LBW.
- Low birth weight /
- Mitochondrial reactive oxygen species /
- Placental angiogenesis /
- Proline metabolism /
- Proline dehydrogenase

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Huang S., Wu D., Chen Z., et al. (2026). Proline-PRODH metabolism promotes placental angiogenesis via the mtROS-STAT3-bFGF/VEGF-A axis. The Innovation Life 4:100233. https://doi.org/10.59717/j.xinn-life.2026.100233

Huang S., Wu D., Chen Z., et al. (2026). Proline-PRODH metabolism promotes placental angiogenesis via the mtROS-STAT3-bFGF/VEGF-A axis. The Innovation Life 4:100233. https://doi.org/10.59717/j.xinn-life.2026.100233

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Proline-PRODH metabolism promotes placental angiogenesis via the mtROS-STAT3-bFGF/VEGF-A axis

GRAPHICAL ABSTRACT

PUBLIC SUMMARY

ABSTRACT