CDDP treatment in mice caused significant testicular damage, including increased permeability and reduced sperm quality.
Cisplatin (CDDP) triggered , indicated by decreased glutathione levels and increased malondialdehyde.
Treatment with human umbilical cord mesenchymal stem cells (hUC-MSCs) restored glutathione levels and normalized ferroptosis-related protein expression.
hUC-MSCs repaired blood-testis barrier integrity and improved sperm quality after CDDP exposure.
In vitro fertilization results showed that hUC-MSCs restored normal embryonic development rates.
Simplified
BACKGROUND: Cisplatin (CDDP), a widely used chemotherapeutic agent, induces reproductive toxicity primarily by damaging the (BTB) and triggering oxidative stress. This study aimed to investigate whether human umbilical cord mesenchymal stem cells (hUC-MSCs) protect against CDDP-induced BTB dysfunction and in mice, with implications for preserving fertility in chemotherapy patients.
METHODS: Male C57 mice were randomized into four groups: control, CDDP-treated, hUC-MSCs-treated, and CDDP+hUC-MSCs-treated. An additional CDDP+Ferrostatin-1 (Fer-1, a ferroptosis inhibitor) group was included to validate ferroptosis involvement. Testicular histology, sperm quality, BTB integrity (via Evans blue permeability assay), and oxidative stress markers were evaluated. Ferroptosis-related (GPX4, NRF2, COX2, TFR1) and BTB-related (N-cadherin, ZO-1, Connexin 43) proteins were assessed by immunofluorescence and Western blotting. In vitro fertilization (IVF) was used to evaluate fertility.
RESULTS: CDDP induced significant testicular damage, reduced sperm quality, increased BTB permeability, and disrupted BTB proteins. It also triggered ferroptosis, as evidenced by decreased GSH, elevated MDA, downregulated GPX4/NRF2, and upregulated COX2/TFR1. hUC-MSCs reversed these changes: restoring GSH levels, reducing MDA, normalizing ferroptosis-related proteins, and repairing BTB integrity. Fer-1 mimicked these effects, confirming ferroptosis as a key mechanism. IVF showed hUC-MSCs restored embryonic development (two-cell and blastocyst rates) to normal.
CONCLUSIONS: hUC-MSCs protect against CDDP-induced reproductive injury by inhibiting ferroptosis (especially in Sertoli cells), repairing BTB, and restoring fertility. Their transient retention and low immunogenicity support their potential as a safe therapeutic strategy for preserving fertility in chemotherapy patients.
Key numbers
Normal levels
Increase in GSH levels
treatment restored GSH levels in -treated mice.
Normal levels
Improvement in embryonic development rates
IVF showed restored two-cell and blastocyst rates to normal.
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Declarations. Ethics approval and consent to participate: The hMSCs used in the study were provided by the Department of Obstetrics at the Yantai Yuhuangding Hospital. The hMSCs were extracted from medical waste (umbilical cords) and donated to our laboratory for the purpose of scientific research. All experimental protocols and procedures including hMSC preparation and animal experiments were approved by the Ethics Committee of Yantai Yuhuangding Hospital (Project title: Experimental study of the effect of human umbilical mesenchymal stem cell on reproductive damage caused by chemotherapy. Approval number: 2021 − 118. Date of approval: 2021.10.28). Consent for publication: Written informed consent for publication was obtained from all participants. Competing interests: The authors declare that they have no competing interests.
PubMed
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