Iranian Journal of Pathology

Dose-Dependent Effects of Intratesticular Adipose-Derived Mesenchymal Stem Cell Injection on Heat-Induced Spermatogenesis Disorder in Wistar Rats: Focus on Apoptosis and Oxidative Stress

Document Type : Original Research

Authors

Maryam Arbabi Dastgerd 1
Saeedeh Shojaeepour 1
Masoud Imani 2
Reza Bahramnezhad 2
Mona Saheli 3
Shahriar Dabiri 4

1 Department of Basic Sciences, Faculty of Veterinary Medicine, Shahid Bahonar University of Kerman, Kerman, Iran

2 Department of Clinical Sciences, Faculty of Veterinary Medicine, Shahid Bahonar University of Kerman, Kerman, Iran

3 Department of Anatomical sciences, Afzalipour Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran

4 Pathology and Stem Cell Research Center, Kerman University of Medical Sciences, Kerman, Iran

https://doi.org/10.30699/ijp.2025.2063503.3477
Abstract
Background & Objective: Spermatogenesis is a temperature-dependent process, and testicular heat stress can cause spermatogenic failure by inducing cell apoptosis and oxidative stress, ultimately leading to male infertility. Adipose-derived mesenchymal stem cells (AMSCs) have been considered an effective therapy for various tissue degenerations, demonstrating the ability to stimulate testicular regeneration and restore spermatogenesis. The current study focuses on the therapeutic potential of AMSCs on semen quality, testicular morphological changes, and oxidative stress parameters in rats exposed to heat stress.
Methods: In this experimental study, 35 adult male rats were randomly assigned to five groups: Group I (control), Group II (vehicle), Group III (heat stress group, temperature-humidity index: 43 °C for 20 minutes), and Groups IV and V (treatment groups receiving 0.5×10⁶ and 1×10⁶ AMSCs, respectively, on the second and fifteenth days after heat stress induction). Sixty days after heat stress exposure, the animals were euthanized; serum testosterone levels and oxidative stress biomarkers were analyzed, and the testes and epididymis were collected for histological and sperm evaluation.
Results: Scrotal heat stress caused deleterious effects on testicular histological structure and function. Testosterone levels and total antioxidant capacity were significantly reduced in the heat stress group. The 1×10⁶ AMSCs-treated group showed moderately preserved testicular tissue morphology. Apoptotic spermatogonia and primary spermatocytes decreased significantly in the AMSCs treatment groups in a dose-dependent manner. Malondialdehyde levels and total antioxidant capacity were also improved. Progressive sperm motility, sperm count, and viability were notably enhanced in the AMSCs-treated groups.
Conclusion: A single dose-dependent injection of AMSCs demonstrated regenerative properties that improved with increasing cell number. Overall, administration of 1×10⁶ AMSCs can alleviate testicular damage and promote the spermatogenesis process in testicular hyperthermia.

Keywords

Mesenchymal Stem Cells
Adipose Tissue
Testis
Hyperthermia
Spermatogenesis
Oxidative Stress
Animal Study

Subjects

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Iranian Journal of Pathology
Volume 21, Issue 1
Winter 2026
Pages 68-79

  • Receive Date 11 June 2025
  • Revise Date 02 July 2025
  • Accept Date 02 August 2025

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