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Amino Acid Restriction Impairs Human Endometrial Stromal Cell Decidualization and Is Rescued by Proline
Chloe Jang1,2,3, Cristiana Iosef3, Stephen J Renaud2,3
1Department of Biochemistry, Western University, London, Canada.
Journal of Cellular and Molecular Medicine
|September 16, 2025
Summary
Maternal amino acid deficiency impairs decidualization, crucial for pregnancy. Proline supplementation, but not leucine, reversed the negative effects of halofuginone-induced stress on human endometrial stromal cells.
Area of Science:
- Reproductive biology
- Cellular and molecular biology
- Biochemistry
Background:
- Decidualization is essential for pregnancy success, involving endometrial stromal cell transformation.
- Maternal amino acid deficiency is linked to impaired decidualization and pregnancy complications.
- Halofuginone (HF) is a compound that induces nutritional stress by mimicking amino acid starvation.
Purpose of the Study:
- To investigate the impact of HF-induced nutritional stress and amino acid supplementation on human endometrial stromal cell (HESC) decidualization.
- To explore the role of specific amino acids, proline and leucine, in mitigating HF's effects on decidualization.
Main Methods:
- Human endometrial stromal cells (HESCs) were exposed to decidualization agents.
- Cells were treated with halofuginone (HF) or leucine-deprived media.
- The effects of proline and leucine supplementation on HF-treated cells were assessed by examining decidualization markers and signaling pathways.
Main Results:
- HF and leucine deprivation inhibited key decidualization markers (e.g., IGFBP-1).
- Proline supplementation, unlike leucine, rescued the inhibitory effects of HF on HESC decidualization.
- HF disrupted transforming growth factor β-SMAD signaling, which was restored by proline.
Conclusions:
- Amino acid availability is critical for proper decidualization.
- Proline plays a vital role in supporting decidualization, potentially counteracting nutritional stress.
- Findings suggest proline supplementation as a therapeutic strategy for improving reproductive health and preventing pregnancy complications.
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