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慢性 THC 给药对雄性小鼠生殖器官、精子和体外受精的影响。

Effect of chronic THC administration in the reproductive organs of male mice, spermatozoa and in vitro fertilization.

机构信息

Dept. of Animal Reproduction, INIA, Madrid, Spain; G.I. Biogénesis, University of Antioquia, Medellín, Colombia.

Dept. of Pharmacology, Faculty of Medicine and Nursing, UPV/EHU, Leioa, Bizkaia and Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain; Dept. of Physiology, Faculty of Medicine and Nursing, UPV/EHU, Leioa, Bizkaia, Spain.

出版信息

Biochem Pharmacol. 2018 Nov;157:294-303. doi: 10.1016/j.bcp.2018.07.045. Epub 2018 Aug 3.

DOI:10.1016/j.bcp.2018.07.045
PMID:30077641
Abstract

The increased use of cannabis as a therapeutic drug in recent years has raised some concerns due to its potential effects on reproductive health. With regards to the male, the endocannabinoid system is involved in the spermatogenesis and in the sperm function. The chronic use of tetrahidrocannabinol (THC) has been associated with sperm anomalies, decreased sperm motility and structural changes in the testis. However, whether THC affects sperms ability to fertilize and to generate embryos remains unclear. The aim of this study was to evaluate this effect using a mice model of THC chronic treatment. For this purpose, a chronic treatment with THC was carried out. Mice were randomly allocated into two groups: an experimental group treated with a daily dose of 10 mg/kg-body weight THC for a period of 30 days and a control group treated with a vehicle. The THC-mice cortex showed a significant decrease of mRNA of Cnr1 compared to control-mice while, in the testis, the expression of Cnr1 was not affected. The weight of testis and epididymis and the histological analysis did not show any change between groups. On the other hand, no changes were observed in the sperm motility or the sperm concentration. The chronic use of THC did not generate any methylation change in the three CpG regions of Cnn1 analysed, neither in the brain nor in the embryos generated by in vitro fertilization (IVF). Finally, the embryo production by IVF was no different using spermatozoa from both THC and control mice. This work contradicts the belief that THC consumption has a negative effect on male reproductive processes.

摘要

近年来,大麻作为一种治疗药物的使用越来越多,由于其对生殖健康的潜在影响,引起了一些关注。就男性而言,内源性大麻素系统参与精子发生和精子功能。慢性使用四氢大麻酚(THC)与精子异常、精子活力下降和睾丸结构变化有关。然而,THC 是否影响精子的受精能力和产生胚胎的能力尚不清楚。本研究旨在使用 THC 慢性治疗的小鼠模型来评估这种影响。为此,进行了 THC 的慢性治疗。将小鼠随机分为两组:实验组每天接受 10mg/kg 体重的 THC 治疗 30 天,对照组给予载体治疗。与对照组相比,THC 处理组的皮质 Cnr1 mRNA 表达显著降低,而睾丸 Cnr1 表达不受影响。睾丸和附睾的重量以及组织学分析显示两组之间没有变化。另一方面,精子活力或精子浓度没有观察到变化。慢性使用 THC 未在大脑或体外受精 (IVF) 产生的胚胎中分析的三个 Cnn1 CpG 区域产生任何甲基化变化。最后,使用来自 THC 和对照组小鼠的精子进行 IVF 产生的胚胎没有差异。这项工作与 THC 消费对男性生殖过程有负面影响的观点相矛盾。

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