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Undescended testis and testicular torsion represent two frequent andrological diseases that affect the pediatric age. Despite these testicular disorders having different causes, they both negatively influence fertility in adulthood mainly due to the accumulation of reactive oxygen species (ROS), which represents the primary molecular damage underlying their long-term effects. The gold standard of treatment for both pathologies is surgery; however, it cannot guarantee an optimal fertility outcome in all clinical cases, underscoring the need to identify effective adjuvant therapies that may target the augmented ROS levels. For this aim, we investigated the pro-proliferative and anti-oxidant effects of PRP (platelet-rich plasma), a hemoderivative product used in regenerative medicine. We confirmed the increased oxidative status in testicular tissue by directly analyzing patients' biopsies with mass spectrometry and highlighting that three antioxidant proteins are significantly overexpressed compared to healthy testicles. Afterward, we in vitro treated cells derived from patients with cryptorchidism or testicular torsion with PRP, showing that it consistently decreases ROS levels and slightly induces cell proliferation. This study supports the potential use of PRP in patients with testis torsion or cryptorchidism, encouraging its future clinical application as adjuvant therapy to preserve the functionality of this organ by decreasing its ROS levels., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical approval: This study was approved by the Ethics Committee of the Azienda Ospedaliera Universitaria Integrata di Verona (Project Number 4159CESC; Protocol Code PRP 3.0). Informed consent was obtained from all patients/parents involved in the study., (© 2024. The Author(s).)

Skeletal muscle exhibits a high regenerative capacity, mainly due to the ability of satellite cells to replicate and differentiate in response to appropriate stimuli. Epigenetic control is effective at different stages of this process. It has been shown that the chromatin-remodeling factor HDAC4 is able to regulate satellite cell proliferation and commitment. However, its molecular targets are still uncovered. To explain the signaling pathways regulated by HDAC4 in satellite cells, we generated tamoxifen-inducible mice with conditional inactivation of HDAC4 in Pax7 + cells (HDAC4 KO mice). We found that the proliferation and differentiation of HDAC4 KO satellite cells were compromised, although similar amounts of satellite cells were found in mice. Moreover, we found that the inhibition of HDAC4 in satellite cells was sufficient to block the differentiation process. By RNA-sequencing analysis we identified P21 and Sharp1 as HDAC4 target genes. Reducing the expression of these target genes in HDAC4 KO satellite cells, we also defined the molecular pathways regulated by HDAC4 in the epigenetic control of satellite cell expansion and fusion.