Ansari Abdul S, Hussain Mubarik, Khan Sadi Rehan, Badar Ayesha, Lohiya N K
1 Department of Zoology, Centre for Advanced Studies, University of Rajasthan, Jaipur, Rajasthan, India.
2 S. S. Jain Subodh College of Global Excellence, Sitapura, Jaipur, Rajasthan, India.
Int J Toxicol. 2018 Nov 1:1091581818809473. doi: 10.1177/1091581818809473.
Reestablishment of fertility, after a male contraceptive method, is of great concern. In this context, RISUG (Reversible Inhibition of Sperm Under Guidance) has been evaluated for its mutagenicity following reversibility with dimethyl sulfoxide (DMSO)/sodium bicarbonate (NaHCO) in Wistar albino rats. Animals were divided into 7 groups, namely, sham-operated control, vas occlusion with RISUG for 90 and 360 days, reversal with DMSO and NaHCO after 90 and 360 days, respectively. The testis, cauda epididymis, cauda epididymal spermatozoa, and serum were evaluated for apoptosis and hormonal status through various assays. RISUG was subjected to Ames test at dose levels of 10, 50, and 100 µL. Results of terminal deoxynucleotidyl transferase nick end labeling and caspase-3 assays in testes and cauda epididymis revealed that the percentage of positive cells in the experimental groups was comparable to sham-operated control. Annexin V assay in cauda epididymal spermatozoa showed slight elevation in group II ( P < 0.05), whereas in the remaining groups, minimum numbers of positive sperms were found. Hormone profile, namely, testosterone, prolactin, cortisol, prostate-specific antigen, and sperm antibody concentration, remained unchanged. In Ames test, no significant increase was observed in the number of revertant colonies on plates containing RISUG in the presence and absence of S9 mix in all 3 strains. Therefore, the reversal of RISUG-induced contraception by solvent vehicle DMSO/NaHCO was successful without any toxicity at the cellular levels.
男性避孕方法之后生育能力的恢复备受关注。在此背景下，已对在Wistar白化大鼠中用二甲基亚砜（DMSO）/碳酸氢钠（NaHCO）进行可逆性处理后的RISUG（引导下精子可逆抑制）进行了致突变性评估。动物被分为7组，即假手术对照组、用RISUG进行输精管闭塞90天和360天的组、分别在90天和360天后用DMSO和NaHCO进行逆转的组。通过各种检测方法对睾丸、附睾尾部、附睾尾部精子和血清的细胞凋亡及激素状态进行了评估。在剂量水平为10、50和100μL时对RISUG进行了艾姆斯试验。睾丸和附睾尾部的末端脱氧核苷酸转移酶缺口末端标记和半胱天冬酶-3检测结果显示，实验组阳性细胞的百分比与假手术对照组相当。附睾尾部精子的膜联蛋白V检测显示，第二组有轻微升高（P<0.05），而在其余组中，发现阳性精子的数量最少。激素水平，即睾酮、催乳素、皮质醇、前列腺特异性抗原和精子抗体浓度，保持不变。在艾姆斯试验中，在所有3个菌株中，无论有无S9混合液，含有RISUG的平板上回复菌落的数量均未观察到显著增加。因此，用溶剂载体DMSO/NaHCO逆转RISUG诱导的避孕是成功的，在细胞水平上没有任何毒性。
