Human hair follicle-derived mesenchymal stem cells improve ovarian function in cyclophosphamide-induced POF mice

Stem Cell Research & Therapy, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 11, 2025

Mesenchymal stem cell (MSCs) of different tissue origins have become a new option for the treatment premature ovarian failure (POF) as they can recovery function. However, there were rarely researches about human hair follicle-derived mesenchymal cells (HF-MSCs) in POF. In this study, we compared effects HF-MSCs and umbilical cord (HU-MSCs) on POF models to explore underlying molecular mechanisms. Female mice received intraperitoneal cyclophosphamid 10 days induce model. One week after drug withdrawal, randomly divided into four groups according tail vein injection drugs, which were: Control group (CON), Premature (POF), (P–H group) HU-MSCs (P–U group). Which Treatment once 4 consecutive times. Serum tissues collected 2 weeks last treatment, fertility was performed by mating. ELISA, HE staining, transmission electron microscopy (TEM) applied evaluate function, oocytes quantity quality, mechanism verified qRT-PCR western blot. addition, tumorigenic risk organs assessed long-term observation. The model successfully established cyclophosphamide 100 mg/kg/d days. Compared with group, two transplantation, serum FSH decreased, AMH E2 increased P–H P–U (p < 0.05), but no significant difference between > 0.05). number primary follicles, secondary follicles antral both significantly while atretic decreased pups lower than that 0. 01). Furthermore, those more mitochondrial ultramicrostructure ovaries showed morphologies number. mitochondria presented spheroids structure fewer numbers, serious vacuolation disordered cristae arrangement. Nevertheless, MSCs transplantation could observe ameliorative alignment vacuolation, well small long rod-like structures. Mechanism study KEAP1 protein expression nuclear translocation NRF2 upregulated downstream HO-1 protein. At last, possibility tumor development excluded observation organ anatomical examination. improve function cyclophosphamide-induced mice, superior HU-MSCs. may inhibiting ferroptosis granulosa through KEAP1/NRF2/HO-1 pathway.

Language: Английский

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Cyclophosphamide induces ovarian granulosa cell ferroptosis via a mechanism associated with HO-1 and ROS-mediated mitochondrial dysfunction

Journal of Ovarian Research, Journal Year: 2024, Volume and Issue: 17(1)

Published: May 18, 2024

Abstract Abnormal granulosa cell (GC) death contributes to cyclophosphamide (CTX) induced primary ovarian insufficiency (POI). To investigate the contribution of GCs POI, gene profiles exposed CTX were assessed using RNA-Seq and bioinformatics analysis. The results showed differentially expressed genes (DEGs) enriched in ferroptosis-related pathway, which is correlated with upregulated heme oxygenase 1 (HO-1) downregulated glutathione peroxidase-4 (GPX4). Using CTX-induced culture (COV434 KGN cells), levels iron, reactive oxygen species (ROS), lipid peroxide, mitochondrial superoxide, morphology membrane potential (MMP) detected by DCFDA, MitoSOX, C11-BODIPY, MitoTracker, Nonylacridine Orange (NAO), JC-1 transmission electron microscopy respectively. iron overload disrupted ROS, including cytoROS, mtROS lipROS homeostasis, associated upregulation HO-1 could induce ferroptosis via dysfunction GCs. Moreover, inhibition suppress GPX4 depletion. This implies a role for ROS highlights effect modulators improving damage, may provide theoretical basis preventing or restoring GC function patients POI.

Language: Английский

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The melatonin-FTO-ATF4 signaling pathway protects granulosa cells from cisplatin-induced chemotherapeutic toxicity by suppressing ferroptosis

Journal of Assisted Reproduction and Genetics, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 10, 2024

In cisplatin-induced premature ovarian failure (POF) mice, granulosa cells showed a high level of ferroptosis. Previous research has indicated that the fat mass and obesity-associated protein/activating transcription factor 4 (FTO/ATF4) axis was involved in regulation The purpose this study to explore role FTO/ATF4 ferroptosis cell.

Language: Английский

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Human umbilical cord mesenchymal stem cells restore chemotherapy-induced premature ovarian failure by inhibiting ferroptosis in vitro ovarian culture system

Reproductive Biology and Endocrinology, Journal Year: 2024, Volume and Issue: 22(1)

Published: Nov. 7, 2024

Mesenchymal stem cells (MSCs) have shown potential in repairing chemotherapy-induced premature ovarian failure (POF). However, challenges such as cell loss and immune phagocytosis post-transplantation hinder their application. Due to easy safe handling, vitro culture is widely available for drug screening, pathophysiological research, fertilization. MSCs could exhibit therapeutic capacity injury, avoid tissue system. Therefore, this study utilizes an system investigate the reparative of human umbilical cord mesenchymal (hUCMSCs) mechanism.

Language: Английский

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