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半胱胺对类固醇激素和能量状态的调节及其对精子发生的影响。

Regulation of steroid hormones and energy status with cysteamine and its effect on spermatogenesis.

作者信息

Wang Yandi, Zhao Yong, Yu Shuai, Feng Yanni, Zhang Hongfu, Kou Xin, Chu Meiqiang, Cui Liantao, Li Lan, Zhang Pengfei, Shen Wei, Min Lingjiang

机构信息

College of Animal Science and Technology, Qingdao Agricultural University, Qingdao 266109, PR China; Key Laboratory of Animal Reproduction and Germplasm Enhancement, Universities of Shandong, Qingdao 266109, PR China.

Key Laboratory of Animal Reproduction and Germplasm Enhancement, Universities of Shandong, Qingdao 266109, PR China; College of Chemistry and Pharmaceutical Sciences, Qingdao Agricultural University, Qingdao 266109, PR China.

出版信息

Toxicol Appl Pharmacol. 2016 Dec 15;313:149-158. doi: 10.1016/j.taap.2016.10.025. Epub 2016 Nov 1.

Abstract

Although it is well known that cysteamine is a potent chemical for treating many diseases including cystinosis and it has many adverse effects, the effect of cysteamine on spermatogenesis is as yet unknown. Therefore the objective of this investigation was to explore the effects of cysteamine on spermatogenesis and the underlying mechanisms. Sheep were treated with vehicle control, 10mg/kg or 20mg/kg cysteamine for six months. After that, the semen samples were collected to determine the spermatozoa motility by computer-assisted sperm assay method. Blood samples were collected to detect the levels of hormones and the activity of enzymes. Spermatozoa and testis samples were collected to study the mechanism of cysteamine's actions. It was found that the effects of cysteamine on spermatogenesis were dose dependent. A low dose (10mg/kg) cysteamine treatment increased ovine spermatozoa motility; however, a higher dose (20mg/kg) decreased both spermatozoa concentration and motility. This decrease might be due to a reduction in steroid hormone production by the testis, a reduction in energy in the testis and spermatozoa, a disruption in the blood-testis barrier, or a breakdown in the vital signaling pathways involved in spermatogenesis. The inhibitory effects of cysteamine on sheep spermatogenesis may be used to model its effects on young male patients with cystinosis or other diseases that are treated with this drug. Further studies on spermatogenesis that focus on patients treated with cysteamine during the peripubertal stage are warranted.

摘要

虽然众所周知半胱胺是治疗包括胱氨酸病在内的多种疾病的有效化学物质,且它有许多不良反应,但半胱胺对精子发生的影响尚不清楚。因此,本研究的目的是探讨半胱胺对精子发生的影响及其潜在机制。给绵羊分别用赋形剂对照、10mg/kg或20mg/kg半胱胺处理6个月。之后,采集精液样本,通过计算机辅助精子分析方法测定精子活力。采集血液样本检测激素水平和酶活性。采集精子和睾丸样本研究半胱胺的作用机制。发现半胱胺对精子发生的影响呈剂量依赖性。低剂量(10mg/kg)半胱胺处理可提高绵羊精子活力;然而,高剂量(20mg/kg)则会降低精子浓度和活力。这种降低可能是由于睾丸类固醇激素分泌减少、睾丸和精子能量减少、血睾屏障破坏或精子发生过程中重要信号通路的中断。半胱胺对绵羊精子发生的抑制作用可用于模拟其对患有胱氨酸病或其他用该药物治疗的疾病的年轻男性患者的影响。有必要对青春期前后用半胱胺治疗的患者的精子发生进行进一步研究。

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