Anandamide modulates human sperm motility: implications for men with asthenozoospermia and oligoasthenoteratozoospermia
Anandamide modulates human sperm motility: implications for men with asthenozoospermia and oligoasthenoteratozoospermia
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DOI：
10.1093/humrep/det232
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发表时间：
2013-08-01
影响因子：
6.1
通讯作者：
Konje, J. C.
中科院分区：
文献类型：
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作者：
Amoako, A. A.;Marczylo, T. H.;Konje, J. C.
人精浆中花生四烯酸乙醇酰胺（AEA）的水平是多少？这些与异常精子有何关系？弱精子症和少弱畸形精子症患者精浆中AEA水平低于正常精子症患者，AEA是一种由膜磷脂合成的生物活性脂质，可能通过大麻素受体（CB 1和CB 2）介导的信号传导，调节精子运动、获能和顶体反应，从而调节人类精子功能和男性生殖。局部AEA水平分别由合成酶和降解酶NAPE-PLD和FAAH调节。内源性信号通路的失调如何影响人类精子功能尚不清楚，这是一项对86名男性进行的横断面研究，他们在一家不孕症诊所接受了为期2年的精液分析，通过超高效液相色谱-串联质谱法对86名志愿者精浆中的AEA进行了定量。采用qRT-PCR方法检测正常精子症、弱精子症、少弱畸形精子症和畸形精子症患者精子中CB 1、CB 2、NAPE-PLD和FAAH的转录水平。正常精子体外暴露于甲酰胺（meth-AEA）以确定其对精子运动力、存活力和线粒体活性的影响。（平均SEM）在弱精子症男性中显著降低（0.080 0.01 nM; P 0.05）或少弱畸形精子症（0.083 0.01 nM; P 0.05）与正常精子症男性（0.198 0.03 nM）相比。此外，与正常精子对照组相比，弱精子症（P 0.001）或少弱畸形精子症（P 0.001）男性精子CB 1 mRNA水平显著降低。超生理水平的meth-AEA可能通过CB 1介导的线粒体活性抑制而降低精子活力和存活力。meth-AEA的抑制作用仅在体外显示，可能无法反映体内发生的情况。由于内源性大麻素系统的调节似乎是维持正常精子功能和男性生育力所必需的，这可能意味着使用大麻会对生殖产生不利影响。外环大麻素，如（9）-四氢大麻酚，很可能与内源性大麻素竞争大麻素受体，扰乱了微妙平衡的内源性大麻素信号系统。内源性大麻素系统的重要性使其成为控制男性生育力的药物干预的有吸引力的靶点。这项工作部分由莱斯特国家卫生服务信托基金大学医院的杂项教育基金资助，以支持莱斯特大学的内源性大麻素研究实验室。作者声明没有竞争利益。
What are the levels of anandamide (N-arachidonoylethanolamide, AEA) in human seminal plasma and how are these related to abnormal spermatozoa?Seminal plasma AEA levels were lower in men with asthenozoospermia and oligoasthenoteratozoospermia compared with normozoospermic men.AEA, a bioactive lipid, synthesized from membrane phospholipids may signal through cannabinoid receptors (CB1 and CB2) to regulate human sperm functions and male reproduction by modulating sperm motility, capacitation and the acrosome reaction in vitro. Local AEA levels are regulated by the synthetic and degradative enzymes, NAPE-PLD and FAAH, respectively. How the deregulation of this endogenous signalling pathway affects human sperm function(s) is not clear.This was a cross-sectional study of 86 men presenting at an infertility clinic for semen analysis over a period of 2 years.AEA was quantified, by ultra-high performance liquid chromatography-tandem mass spectrometry, in seminal plasma from 86 volunteers. Using qRTPCR, CB1, CB2, NAPE-PLD and FAAH transcript levels were determined in spermatozoa from men with normozoospermia, asthenozoospermia, oligoasthenoteratozoospermia and teratozoospermia. Normal spermatozoa were exposed in vitro to methanadamide (meth-AEA) to determine its effect on sperm motility, viability and mitochondrial activity.Seminal plasma AEA levels (mean SEM) were significantly lower in men with asthenozoospermia (0.080 0.01 nM; P 0.05) or oligoasthenoteratozoospermia (0.083 0.01 nM; P 0.05) compared with normozoospermic men (0.198 0.03 nM). In addition, the levels of spermatozoal CB1 mRNA were significantly decreased in men with asthenozoospermia (P 0.001) or oligoasthenoteratozoospermia (P 0.001) compared with normozoospermic controls. Supra-physiological levels of meth-AEA decreased sperm motility and viability, probably through CB1-mediated inhibition of mitochondrial activity.The inhibitory effect of meth-AEA was only shown in vitro and may not reflect what happens in vivo.As the regulation of the endocannabinoid system appears to be necessary for the preservation of normal sperm function and male fertility, there may be implications for the adverse reproductive consequences of marijuana use. Exocannabinoids, such as (9)-THC, are likely to compete with endocannabinoids at the cannabinoid receptors, upsetting the finely balanced endocannabinoid signalling system. The importance of the endocannabinoid system makes it an attractive target for pharmacological interventions to control male fertility.This work was funded in part by miscellaneous educational funds from the University Hospitals of Leicester National Health Services Trust to support the Endocannabinoid Research Laboratory of University of Leicester. The authors declare no competing interests.