# 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

## TL;DR

Injecting a higher dose of fat-derived stem cells helps reduce testicular damage and improve sperm production in rats exposed to heat stress.

## Contribution

This study demonstrates the dose-dependent regenerative effects of adipose-derived mesenchymal stem cells in heat-induced spermatogenesis disorders.

## Key findings

- Higher AMSC doses improved testicular tissue structure and reduced apoptosis in heat-stressed rats.
- AMSC treatment enhanced sperm motility, count, and viability in a dose-dependent manner.
- Oxidative stress biomarkers were significantly improved with AMSC administration.

## Abstract

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.

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.

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.

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.