Ansari A S, Hussain M, Khan S R, Lohiya N K
Department of Zoology, Centre for Advanced Studies, University of Rajasthan, Jaipur, India.
Andrology. 2016 Mar;4(2):306-13. doi: 10.1111/andr.12155. Epub 2016 Jan 8.
Among the vas-based methods on trial, reversible inhibition of sperm under guidance (RISUG(®) ), a co-polymer of styrene and maleic anhydride is being projected as an effective alternative to No Scalpel Vasectomy. RISUG offers long-term contraception with safety, efficacy in human trials and can be delivered by no-scalpel injection. Currently, the procedure is under phase-III clinical trial. However, reversal of this vas-based drug-induced contraception needs to be established in animal models prior to clinical trials to ensure its claim as an effective alternative for vasectomy. In the present investigation, the relative suitability of dimethyl sulphoxide (DMSO) and NaHCO3 for RISUG induced long-term vas occlusion reversal was carried out in albino rats. Animals were allocated into four groups (n = 10), viz., sham-operated control (group-I), vas occlusion with RISUG for 360 days (group-II), vas occlusion with RISUG for 360 days and reversal with DMSO (group-III) and vas occlusion with RISUG for 360 days and reversal with NaHCO3 (group-IV). A variable response in fertility was observed in different groups. Absolute sterility in group III at all mating intervals, while, zero percent fertility in groups II and IV following 90 days of occlusion was observed. Following reversal restoration of fertility with DMSO at 45 days, whereas, reversal by NaHCO3 at 30 days was noticed. Ejaculated spermatozoa of RISUG injected and initial intervals of reversed animals exhibited various degrees of abnormalities. The testes exhibited focal degeneration in vas occluded animals. The occluded lumen of the vas deferens contained an eosinated polymer with exfoliated epithelium. Following vas occlusion reversal, a complete regeneration in the vas epithelium was seen. All other parameters remained unaltered. The reversal with NaHCO3 resulted into an early resumption of fertility when compared with DMSO and the procedure found to be successful, feasible and safe up to F1 generation. Thus, RISUG provides a hope for reversible male contraceptives.
在正在试验的基于输精管的方法中,在引导下对精子进行可逆抑制(RISUG(®)),一种苯乙烯和马来酸酐的共聚物,正被视为无刀输精管切除术的有效替代方法。RISUG能提供长期避孕效果,在人体试验中具有安全性和有效性,并且可以通过无刀注射进行。目前,该程序正处于三期临床试验阶段。然而,在进行临床试验之前,需要在动物模型中确定这种基于输精管的药物诱导避孕方法的可逆性,以确保其作为输精管切除术的有效替代方法的说法成立。在本研究中,在白化大鼠中进行了二甲基亚砜(DMSO)和碳酸氢钠(NaHCO₃)对RISUG诱导的长期输精管阻塞逆转的相对适用性研究。将动物分为四组(n = 10),即假手术对照组(第一组)、用RISUG进行输精管阻塞360天(第二组)、用RISUG进行输精管阻塞360天并用DMSO进行逆转(第三组)以及用RISUG进行输精管阻塞360天并用NaHCO₃进行逆转(第四组)。在不同组中观察到生育能力的可变反应。第三组在所有交配间隔均绝对不育,而在阻塞90天后,第二组和第四组的生育能力为零。用DMSO逆转后,在45天时恢复生育能力,而用NaHCO₃逆转则在30天时观察到。注射RISUG后的射精精子以及逆转动物的初始间隔显示出不同程度的异常。在输精管阻塞的动物中,睾丸出现局灶性变性。输精管的阻塞管腔含有嗜酸性聚合物和脱落的上皮细胞。输精管阻塞逆转后,可见输精管上皮完全再生。所有其他参数保持不变。与DMSO相比,用NaHCO₃逆转导致生育能力更早恢复,并且该程序在F1代之前被发现是成功、可行且安全的。因此,RISUG为可逆性男性避孕药提供了希望。