Montik Nina, Crescenzi Daniele, Marzocchini Carolina, Lubinski Irene, Grementieri Linda, Peruzzi Sonia, Lombó Marta, Ciavattini Andrea, Carnevali Oliana
Gynecologic Section, Department of Odontostomatologic and Specialized Clinical Sciences, Università Politecnica delle Marche, 60123 Ancona, Italy.
Department of Molecular Biology, Universidad de León, 24071 León, Spain.
Int J Mol Sci. 2025 Apr 23;26(9):3996. doi: 10.3390/ijms26093996.
The endocannabinoid system (ECS) is a complex endocrine network involved in maintaining body homeostasis. It comprises endocannabinoids, their receptors (CB1 and CB2), and the enzymes and transporters responsible for their synthesis and degradation. While the ECS's role in the nervous system is well established, its functions in other organs and peripheral tissues, including the cardiovascular, gastrointestinal, and reproductive systems, remain incompletely understood. With the increasing use of marijuana, particularly among individuals of reproductive age, concerns have emerged regarding its potential impact on male and female fertility. Phytocannabinoids (∆9tethrahydrocannabinol and cannabidiol), as well as synthetic cannabimimetic drugs, interact with the ECS, influencing sperm and oocyte physiology and reproductive outcomes. Recent research has identified ECS-related biomarkers with potential applications in infertility diagnosis, particularly in assessing male fertility with greater precision. Furthermore, emerging evidence suggests that ECS signaling pathways are involved in epigenetic modifications, which may influence health maintenance, disease susceptibility, and transgenerational inheritance patterns. These findings highlight the therapeutic potential of ECS modulation in reproductive disorders and broader medical applications. This narrative review aims to elucidate the role of the ECS in human reproduction, with a particular focus on the influence of endocannabinoids on gametogenesis. While current research underscores the critical role of the ECS in fertility, further investigations are needed to fully elucidate its underlying mechanisms and its broader implications for reproductive health and therapeutic interventions.
内源性大麻素系统（ECS）是一个复杂的内分泌网络，参与维持身体的内环境稳定。它由内源性大麻素、其受体（CB1和CB2）以及负责其合成和降解的酶和转运体组成。虽然ECS在神经系统中的作用已得到充分证实，但其在包括心血管、胃肠道和生殖系统在内的其他器官和外周组织中的功能仍未完全了解。随着大麻使用的增加，尤其是在育龄人群中，人们对其对男性和女性生育能力的潜在影响产生了担忧。植物大麻素（Δ9-四氢大麻酚和大麻二酚）以及合成大麻素类药物与ECS相互作用，影响精子和卵母细胞的生理功能以及生殖结果。最近的研究已经确定了与ECS相关的生物标志物，这些标志物在不孕症诊断中具有潜在应用，特别是在更精确地评估男性生育能力方面。此外，新出现的证据表明，ECS信号通路参与表观遗传修饰，这可能影响健康维持、疾病易感性和跨代遗传模式。这些发现凸显了ECS调节在生殖障碍和更广泛医学应用中的治疗潜力。这篇叙述性综述旨在阐明ECS在人类生殖中的作用，特别关注内源性大麻素对配子发生的影响。虽然目前的研究强调了ECS在生育中的关键作用，但仍需要进一步研究以充分阐明其潜在机制及其对生殖健康和治疗干预的更广泛影响。
