Signorini Cinzia, Moretti Elena, Liguori Laura, Marcucci Caterina, Durand Thierry, Galano Jean-Marie, Oger Camille, Collodel Giulia
Department of Molecular and Developmental Medicine, University of Siena, Policlinico Le Scotte, 53100 Siena, Italy.
Institut des Biomolécules Max Mousseron (IBMM), Pole Chimie Balard Recherche, UMR 5247, CNRS, Université de Montpellier, ENSCM, 34090 Montpellier, France.
Int J Mol Sci. 2025 Jul 26;26(15):7231. doi: 10.3390/ijms26157231.
F-Neuroprostanes (F-NeuroPs), oxidative metabolites of docosahexaenoic acid, act as bioactive lipid mediators enhancing sperm motility and induce capacitation-like changes in vitro. Their biological action is proposed to involve sperm ion channels, in particular ryanodine receptors (RyRs), which regulate intracellular calcium homeostasis. We evaluated the effects of dantrolene, a RyR inhibitor, on motility and vitality of a selected spermatozoa at different concentrations (10, 30, 50, 100 μM). Then sperm motility, acrosome integrity, and RyR localization following co-incubation with dantrolene (D50 or D100 μM) and 4-/10-F-NeuroPs (7 ng) were investigated. Acrosomal status was assessed using agglutinin (PSA) staining and RyR localization by immunofluorescence. D50 was identified as the minimum effective dose to induce significant reductions in sperm motility. F-NeuroPs significantly increased rapid progressive motility versus controls. Co-incubation with F-NeuroPs + D50 reduced rapid motility and increased in situ and circular movement. The acrosome staining appeared altered or absent to different percentages, and RyR localization was also seen in the midpiece. These findings suggested that F-NeuroPs enhance sperm motility via RyR-mediated pathways, as confirmed by dantrolene inhibition. Accordingly, our results underscore the physiological relevance of RyRs in sperm function and suggest new insights into lipid-based mechanisms regulating sperm motility.
F-神经前列腺素（F-NeuroPs）是二十二碳六烯酸的氧化代谢产物，作为生物活性脂质介质可增强精子活力并在体外诱导类似获能的变化。其生物学作用被认为涉及精子离子通道，特别是调节细胞内钙稳态的兰尼碱受体（RyRs）。我们评估了RyR抑制剂丹曲林在不同浓度（10、30、50、100μM）下对选定精子活力和活力的影响。然后研究了与丹曲林（D50或D100μM）和4-/10-F-NeuroPs（7 ng）共同孵育后的精子活力、顶体完整性和RyR定位。使用凝集素（PSA）染色评估顶体状态，通过免疫荧光评估RyR定位。D50被确定为诱导精子活力显著降低的最小有效剂量。与对照组相比，F-NeuroPs显著增加了快速进行性运动。与F-NeuroPs + D50共同孵育降低了快速运动，并增加了原位和圆周运动。顶体染色出现不同百分比的改变或缺失，并且在中段也可见RyR定位。这些发现表明F-NeuroPs通过RyR介导的途径增强精子活力，丹曲林抑制证实了这一点。因此，我们的结果强调了RyRs在精子功能中的生理相关性，并为调节精子活力的脂质机制提供了新的见解。
