ArticleCellular & molecular biology letters2025
Human urine stem cells protect against cyclophosphamide-induced premature ovarian failure by inhibiting SLC1A4-mediated outflux of intracellular serine in ovarian granulosa cells.
Article in Cellular & molecular biology letters, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Applications of Exosomes in Female Medicine: A Systematic Review of Molecular Biology, Diagnostic and Therapeutic Perspectives.International journal of molecular sciences · 2026Pooled it
- Article
- Gut microbiota-derived Tryptophanol driven by N-Carbamylglutamate alleviates premature ovarian failure through inhibiting oxidative stress.Journal of ovarian research · 2026Article
- Research based on serine metabolism indicates mesenchymal stem cells alleviate psoriasis by regulating the PSPH-PINK1-Parkin-NLRP3 pathway in HaCaT.Stem cell research & therapy · 2026Article
- Article
- HuMSCs-derived exosomes alleviate premature ovarian insufficiency by enhancing SIRT3-mediated mitochondrial function in theca-interstitial cells.Journal of ovarian research · 2026Article
- Serine inhibits granulosa cell ferroptosis to maintain ovarian function.Nature communications · 2026Article
- Integrated network toxicology and multi-omics profiling reveal cell cycle, DNA damage repair, and metabolic alterations in cyclophosphamide-induced premature ovarian insufficiency.Frontiers in pharmacology · 2026Article
- Protective effect of a novel hydrogel loaded with CM-UCMSCs on vitrified-thawed ovaries during in vitro culture.Frontiers in bioengineering and biotechnology · 2026Article
- Roles of exosomes in microenvironment-related premature ovarian insufficiency: mechanisms and therapeutic intervention.Reproductive biology and endocrinology : RB&E · 2025Review
- Human urine-derived stem cells alleviate psoriasis by suppressing JAK2/STAT3 pathway-mediated macrophage polarization.Stem cell research & therapy · 2025Article
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9 authors.
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Abstract
backgroundCyclophosphamide (CTX) is the first-line medication for the treatment of breast cancer, although it potentially leads to severe ovarian dysfunction and even premature ovarian failure (POF). However, the mechanism of CTX-induced POF remains unclear. Mesenchymal stem cell-based therapy has been wildly used for treating numerous diseases. Therefore, our study aims to elucidate the underlying mechanism of CTX-induced POF and to explore the therapeutic effect of human urine stem cells (hUSCs) in POF.
methodsCTX-induced POF or ovarian granulosa cell (GCs) apoptosis were treated with hUSCs and their exosomes in vitro and in vivo. Morphological, histological, and functional alternations were examined using multiple approaches. The effector molecules of hUSC-derived exosomes (hUSC-Exo) were determined by differential expression analysis in the ovaries. The target genes of miRNA were accessed by transcriptome sequencing in GCs, and the underlying mechanisms were further elucidated.
resultshUSCs remarkably inhibited CTX-induced apoptosis and promoted the proliferation of GCs, respectively. In addition, we observed that miR-27b-3p was highly expressed in hUSC-Exo and markedly suppressed CTX-induced GC apoptosis by specifically inhibiting the expression of SLC1A4, a serine transporter, in ovarian GCs, which, in turn, elevated the concentration of the intracellular serine by inhibiting the outflux of cellular serine. More importantly, the knockdown of SLC1A4 or simple supplementation of serine suppressed CTX-induced apoptosis of GCs. Finally, we demonstrated that CTX-induced apoptosis of ovarian GCs was essential for POF by reducing the intracellular serine concentration via elevating the expression of SLC1A4, whereas hUSCs protected against CTX-induced POF via miR-27b-3p/SLC1A4/serine axis-mediated activation of the PI3K/AKT/mTOR signaling pathway.
conclusionsOur study suggests that hUSC-based cell therapy or simple supplementation of serine may provide an efficient therapeutic approach for the prevention and treatment of CTX-induced POF clinically.
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