Liu Huang, Chen Xuren, Feng Xin, Zhu Zhiyong, Liao Zhiwei, Zhu Shenghui, Pang Tao, Ren Xuejun, Yang Ruilin
Department of Andrology, National Health Commission (NHC) Key Laboratory of Male Reproduction and Genetics, Guangdong Provincial Reproductive Science Institute (Guangdong Provincial Fertility Hospital), Human Sperm Bank of Guangdong Province, Guangzhou, Guangdong, 510600, People's Republic of China.
Department of Andrology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, 510080, People's Republic of China.
Drug Des Devel Ther. 2025 Sep 4;19:7777-7794. doi: 10.2147/DDDT.S522738. eCollection 2025.
Spermatogenesis is a complex process that affects the outcome of fertility. Different types of cellular metabolic processes have both positive and negative effects on sperm production. Exploring new methods to promote spermatogenesis is the best way to improve fertility. This study confirmed the effect of astaxanthin on promoting spermatogenesis through various experiments.
To explore new activities of astaxanthin and develop the new methods to promote spermatogenesis.
Network pharmacology, in vitro cell culture and in vivo experiments were used in this research. The targets and potential signaling pathways of astaxanthin in the treatment of spermatogenesis, the effects on the proliferation and apoptosis of spermatogonial stem cells, and the therapeutic effect on oligoasthenozoospermia in mice induced with cyclophosphamide of astaxanthin were all observed. The ACSL3, VDAC, GPX4, FADS2, GLS2, Steap3, MDA, GSH-Px, and iron ions were detected and analyzed to reveal the potential regulatory mechanisms.
Astaxanthin has 52 key targets for treating spermatogenesis, among which the oxidative stress metabolic pathway is one of the most important factors. The sperm concentration and forward motility of the oligoasthenozoospermia model mice fed with astaxanthin were significantly greater than those of the control group. The proliferation rate of spermatogonial stem cells cultured with astaxanthin was also significantly greater than that of quercetin group and the proportion of apoptotic cells was significantly lower. Astaxanthin can reduce ACSL3, MDA, and iron ions in spermatogonial stem cells; increase the expression of Steap3, VDAC, GPX4, GLS2, GSH-Px, and FADS2; and improve ester metabolism to promote spermatogenesis in oligoasthenozoospermia model mice.
Astaxanthin can regulate the metabolism of fatty acid through the ferroptosis pathway, and reduce the mitochondrial oxidative stress damage, and further regulate FADS2, Steap3, and other factors to promote spermatogenesis.
精子发生是一个影响生育结果的复杂过程。不同类型的细胞代谢过程对精子生成既有积极影响也有消极影响。探索促进精子发生的新方法是提高生育能力的最佳途径。本研究通过各种实验证实了虾青素对促进精子发生的作用。
探索虾青素的新活性并开发促进精子发生的新方法。
本研究采用网络药理学、体外细胞培养和体内实验。观察虾青素治疗精子发生的靶点和潜在信号通路、对精原干细胞增殖和凋亡的影响以及对环磷酰胺诱导的小鼠少弱精子症的治疗作用。检测并分析ACSL3、VDAC、GPX4、FADS2、GLS2、Steap3、MDA、GSH-Px和铁离子，以揭示潜在的调控机制。
虾青素治疗精子发生有52个关键靶点，其中氧化应激代谢途径是最重要的因素之一。喂食虾青素的少弱精子症模型小鼠的精子浓度和前向运动能力显著高于对照组。用虾青素培养的精原干细胞的增殖率也显著高于槲皮素组，凋亡细胞比例显著降低。虾青素可降低精原干细胞中的ACSL3、MDA和铁离子；增加Steap3、VDAC、GPX4、GLS2、GSH-Px和FADS2的表达；改善酯代谢，促进少弱精子症模型小鼠的精子发生。
虾青素可通过铁死亡途径调节脂肪酸代谢，减轻线粒体氧化应激损伤，并进一步调节FADS2、Steap3等因子以促进精子发生。
