MORPHOLOGICAL AND FUNCTIONAL CHANGES INDUCED BY THE CHEMOTHERAPEUTIC AGENT 5-FLUOROURACIL IN THE MURINE TESTIS: AN INTEGRATIVE REVIEW

5-Fluorouracil (5-FU) is a widely used antimetabolite chemotherapeutic agent whose cytotoxic effects extend beyond malignant tissues and particularly affect highly proliferative organs such as the testes. Experimental evidence indicates that 5-FU induces significant morphological, functional, endocrine, and molecular alterations in the male reproductive system, potentially compromising fertility. This integrative review summarizes and critically analyzes experimental studies published between 2020 and 2025 evaluating the effects of 5-FU on rodent testes, with a focus on species and strains, histological damage, oxidative stress, mitochondrial dysfunction, inflammation, hormonal dysregulation, apoptosis, and DNA damage. In addition, the review discusses compounds investigated for their potential to mitigate 5-FU-induced testicular toxicity. Collectively, the findings reveal that 5-FU consistently compromises testicular structure and function through convergent mechanisms involving oxidative stress, mitochondrial dysfunction, and hormonal imbalance. Although antioxidant and anti-inflammatory interventions attenuate some of these effects, the lack of standardized protocols remains a major barrier to clinical translation.