Phosphodiesterase 10A inhibitor PF-2545920 as a prospective agent for the clinical promotion of sperm motility.

IF 3 2区 医学 Q2 ANDROLOGY
Asian Journal of Andrology Pub Date : 2023-09-01 Epub Date: 2023-04-04 DOI:10.4103/aja2022117
Yi-Ting Yang, Bin Yan, Yu-Hua Li, Li-Na Guo, Wei-Wei Wang, Li-Jie Liu, He-Guo Yu, Hua Diao
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Abstract

Phosphodiesterase (PDE) inhibitors can improve sperm motility in patients with asthenozoospermia. However, the most commonly reported nonselective PDE inhibitor pentoxifylline and PDE5 inhibitor sildenafil have the disadvantages of requiring a high concentration and destroying sperm integrity. We examined the PDE10A inhibitor PF-2545920 to compare its ability to promote sperm motility with that of pentoxifylline and sildenafil. After seminal plasma was discarded, several semen samples were subjected to four treatments (control, PF-2545920, pentoxifylline, and sildenafil) to evaluate their ability to affect motility, viability, and spontaneous acrosome reactions. Intracellular calcium and adenosine triphosphate (ATP), mitochondrial membrane potential, and penetration through viscous medium were assessed by flow cytometry, luciferase, and hyaluronic acid after treatment with PF-2545920. Statistical analyses were performed using the analysis of variance statistical test. PF-2545920 elevated the percentage of motile spermatozoa compared to the control, pentoxifylline, and sildenafil groups at 10 µmol l -1 ( P < 0.01). It is less toxic to GC-2spd mouse spermatocytes cells and spermatozoa and causes fewer spontaneous acrosomal reactions ( P < 0.05). PF-2545920 also increased mitochondrial membrane potential ( P < 0.001) and altered intracellular calcium ( P < 0.05) in a dose-dependent manner, including increasing sperm hyaluronic acid penetrating ability ( P < 0.05). Therefore, PF-2545920 might be an excellent choice for stimulating the sperm motility.

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磷酸二酯酶10A抑制剂PF-2545920作为临床促进精子活力的前瞻性药物。
磷酸二酯酶(PDE)抑制剂可以改善弱精子症患者的精子活力。然而,最常见的非选择性PDE抑制剂己酮可可碱和PDE5抑制剂西地那非具有需要高浓度和破坏精子完整性的缺点。我们检测了PDE10A抑制剂PF-2545920,以比较其与己酮可可碱和西地那非促进精子运动的能力。丢弃精浆后,对几个精液样本进行四种处理(对照组,PF-2545920、己酮可可碱和西地那非),以评估其影响运动能力、活力和自发顶体反应的能力。PF-2545920处理后,通过流式细胞术、荧光素酶和透明质酸评估细胞内钙和三磷酸腺苷(ATP)、线粒体膜电位以及通过粘性介质的渗透性。采用方差分析法进行统计分析。PF-2545920与对照组己酮可可碱相比提高了活动精子的百分比,和10µmol l-1的西地那非组(P<0.01)。它对GC-2spd小鼠精母细胞和精子的毒性较小,引起的自发顶体反应较少(P<0.05)。PF-2545920还以剂量依赖的方式增加线粒体膜电位(P<0.001)和改变细胞内钙(P<0.05),包括提高精子透明质酸穿透能力(P<0.05)。因此,PF-2545920可能是刺激精子活力的良好选择。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Asian Journal of Andrology
Asian Journal of Andrology 医学-泌尿学与肾脏学
CiteScore
4.90
自引率
3.40%
发文量
2252
审稿时长
2.2 months
期刊介绍: Fields of particular interest to the journal include, but are not limited to: -Sperm biology: cellular and molecular mechanisms- Male reproductive system: structure and function- Hormonal regulation of male reproduction- Male infertility: etiology, pathogenesis, diagnosis, treatment and prevention- Semen analysis & sperm functional assays- Sperm selection & quality and ART outcomes- Male sexual dysfunction- Male puberty development- Male ageing- Prostate diseases- Operational andrology- HIV & male reproductive tract infection- Male contraception- Environmental, lifestyle, genetic factors and male health- Male reproductive toxicology- Male sexual and reproductive health.
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