Kaltsas Aris, Dimitriadis Fotios, Zachariou Athanasios, Sofikitis Nikolaos, Chrisofos Michael
Third Department of Urology, Attikon University Hospital, School of Medicine, National and Kapodistrian University of Athens, 12462 Athens, Greece.
Department of Urology, Faculty of Medicine, School of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.
Cells. 2025 Jan 15;14(2):120. doi: 10.3390/cells14020120.
Phosphodiesterases, particularly the type 5 isoform (PDE5), have gained recognition as pivotal regulators of male reproductive physiology, exerting significant influence on testicular function, sperm maturation, and overall fertility potential. Over the past several decades, investigations have expanded beyond the original therapeutic intent of PDE5 inhibitors for erectile dysfunction, exploring their broader reproductive implications. This narrative review integrates current evidence from in vitro studies, animal models, and clinical research to clarify the roles of PDEs in effecting the male reproductive tract, with an emphasis on the mechanistic pathways underlying cyclic nucleotide signaling, the cellular specificity of PDE isoform expression, and the effects of PDE5 inhibitors on Leydig and Sertoli cell functions. Although certain findings suggest potential improvements in sperm motility, semen parameters, and a more favorable biochemical milieu for spermatogenesis, inconsistencies in study design, limited sample sizes, and inadequate long-term data temper definitive conclusions. Addressing these gaps through standardized protocols, larger and more diverse patient cohorts, and explorations of mechanistic biomarkers could pave the way for incorporating PDE5 inhibitors into evidence-based fertility treatment strategies. In the future, such targeted approaches may inform individualized regimens, optimize male reproductive outcomes, and refine the clinical application of PDE5 inhibitors as part of comprehensive male fertility management.
磷酸二酯酶，特别是5型同工酶（PDE5），已被公认为男性生殖生理学的关键调节因子，对睾丸功能、精子成熟和整体生育潜力具有重大影响。在过去几十年中，研究范围已超越PDE5抑制剂治疗勃起功能障碍的最初治疗意图，探索其更广泛的生殖意义。这篇叙述性综述整合了来自体外研究、动物模型和临床研究的现有证据，以阐明磷酸二酯酶在影响男性生殖道方面的作用，重点关注环核苷酸信号传导的机制途径、PDE同工型表达的细胞特异性以及PDE5抑制剂对睾丸间质细胞和支持细胞功能的影响。尽管某些研究结果表明精子活力、精液参数可能得到改善，以及精子发生的生化环境更有利，但研究设计的不一致、样本量有限以及长期数据不足影响了确定性结论。通过标准化方案、更大和更多样化的患者队列以及对机制生物标志物的探索来填补这些空白，可能为将PDE5抑制剂纳入基于证据的生育治疗策略铺平道路。未来，这种有针对性的方法可能为个体化治疗方案提供依据，优化男性生殖结局，并完善PDE5抑制剂作为男性综合生育管理一部分的临床应用。
