Effects of Amino Acid Restriction on Decidualization of Human Endometrial Stromal Cells

This study aimed to evaluate the effects of amino acid restriction, as mimicked by Halofuginone (HF), and amino acid supplementation on decidualization of human endometrial stromal cells (HESCs). When HESCs were exposed to decidualization agents, distinct morphological changes and increased insulin-like growth factor binding protein 1 (IGFBP-1) production were observed, indicative of successful decidualization. HF treatment inhibited IGFBP-1 secretion and expression of key decidualization markers in a dose-dependent manner. Supplementation with proline, but not leucine, rescued the inhibitory effects of HF on decidualization of HESCs. RNA-sequencing analysis revealed that several growth factors crucial for decidualization were inhibited by HF, suggesting their sensitivity to amino acid availability. HF disrupted transforming growth factor β (TGFβ)-SMAD signaling, which was restored by proline supplementation. To assess the effect of amino acid restriction on the process of decidualization, immortalized human endometrial stromal cells were treated with decidualization agents, cyclic AMP and medroxyprogesterone acetate, in the presence or absence of Halofuginone (HF).