Soltanineghad M, Roshan-Milani S, Saboory E, Kheradmand F, Pourheydar M, Pourheydar B, Motazakker M, Chodari L
Bratisl Lek Listy. 2019;120(4):277-283. doi: 10.4149/BLL_2019_041.
The opioid system may exert positive direct and/or indirect effects on spermatogenesis at multiple levels including the levels of the central nervous system and at the testes/sperm levels. However, long term opioid use could be associated with several reproductive complications that place the users at risk of hypogonadism and even infertility. There is little available information regarding the contribution of opioids and their apoptotic effects on testis Sertoli cells. Here, the effects of DAMGO (mu opioid receptor's agonist), DPDPE (delta opioid receptor's agonist) and DYN 1-9 (kappa opioid receptor's agonist) on Sertoli cell viability and apoptosis were investigated.
Cultured Sertoli cells were exposed to each agonist (0.1-100 µM, for 24 or 48 hours) and their apoptotic effects were investigated.
Cell viability was decreased and apoptosis was increased in the cells exposed to DAMGO in a concentration-dependent manner, while in the cells exposed to DPDPE, no significant changes were observed. In cells exposed to DYN 1-9, the viability did not significantly change, however apoptosis increased significantly, following the exposure to the high concentration of DYN 1-9.
These data suggest that mu and Kappa, but not delta receptors mediated apoptosis in Sertoli cells may be involved, at least in part, in testicular homeostasis and/or reproductive dysfunction (Tab. 1, Fig. 3, Ref. 52).
阿片类系统可能在多个层面,包括中枢神经系统层面以及睾丸/精子层面,对精子发生产生直接和/或间接的积极影响。然而,长期使用阿片类药物可能会引发多种生殖并发症,使使用者面临性腺功能减退甚至不育的风险。关于阿片类药物及其对睾丸支持细胞的凋亡作用的相关信息甚少。在此,研究了DAMGO(μ阿片受体激动剂)、DPDPE(δ阿片受体激动剂)和DYN 1-9(κ阿片受体激动剂)对支持细胞活力和凋亡的影响。
将培养的支持细胞暴露于每种激动剂(0.1 - 100 μM,持续24或48小时),并研究其凋亡作用。
暴露于DAMGO的细胞中,细胞活力下降,凋亡增加,且呈浓度依赖性;而暴露于DPDPE的细胞未观察到显著变化。暴露于DYN 1-9的细胞,其活力无显著变化,但在暴露于高浓度DYN 1-9后,凋亡显著增加。
这些数据表明,μ和κ受体而非δ受体介导的支持细胞凋亡可能至少部分参与了睾丸内环境稳定和/或生殖功能障碍(表1,图3,参考文献52)。