Toxicity and Mutagenicity Evaluation Following RISUG Contraception Reversal in Rats

Abstract

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 (NaHCO3) 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 NaHCO3 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/NaHCO3 was successful without any toxicity at the cellular levels.

Safety & efficacy of an intravasal, one-time injectable & non-hormonal male contraceptive (RISUG)

“…RISUG affects the sperm membrane including the acrosome which may have resulted in the sperm losing its fertilizing ability222324. Successful reversal of RISUG injection has been observed in rat, rabbit and langur monkeys’ studies without any side effects2526272829303132. However, reversibility of fertilizing ability of sperms was not attempted in this study.…”

RISUG® as a male contraceptive: journey from bench to bedside

“…It is also concluded that vas occlusion with RISUG ® at the contraceptive dose regimen is not associated with genotoxicity in leukocytes or the testis of pre-and post-reversal rats [61]. The study using both DMSO and NaHCO 3 for reversal of RISUG ® -induced contraception was successful without any toxicity at the cellular levels [62]. ii.…”

Preparing for sperm‐targeted contraception: College students’ perceptions and intentions related to non‐hormonal intravas injectable gel

“…Currently, there are two NH-IVIG prototypes: Vasalgel and reversible inhibition of sperm under guidance (RISUG). The flexible, clear-colored hydrogels are composed of dimethyl sulfoxide and dissolved styrene-alt-maleic acid (Vasalgel) or styrene-alt-maleic anhydride with or without iron oxide and copper (RISUG) (Ansari, Hussain, Khan, Badar, & Lohiya, 2018;Colagross-Schouten, Lemoy, Keesler, Lissner, & VandeVoort, 2017;Jha, Jha, & Guha, 2009;Waller, Bolick, Lissner, Premanandan, & Gamerman, 2016). NH-IVIG is administered via an outpatient procedure wherein a medical professional performs minimally invasive, no-scalpel scrotal incisions and bilaterally injects NH-IVIG into a section of the lumen of each vas deferens (Ansari, Hussain, Khan, & Lohiya, 2016;Kanakis & Goulis, 2015).…”

“…Early NH-IVIG data show efficacy percentages comparable to available LARCs and confirmed single doses can possibly last one year (Vasalgel) to over a decade (RISUG) (Colagross-Schouten et al, 2017; Kanakis & Goulis, 2015;Waller et al, 2016;Waller, Bolick, Lissner, Premanandan, & Gamerman, 2017). Reversibility through urethral expulsion has been achieved by sodium bicarbonate flushes, applying vibration and palpation, or heating with microwaves Ansari, Hussain, et al, 2018;Jha et al, 2009;Waller et al, 2017). NH-IVIGs have shown minor local side effects, tested negative for genotoxicity or mutagenicity, and generated fewer complications than other experimental methods or vasectomies Ansari, Hussain, et al, 2018;Colagross-Schouten et al, 2017;Waller et al, 2016Waller et al, , 2017.…”

“…Reversibility through urethral expulsion has been achieved by sodium bicarbonate flushes, applying vibration and palpation, or heating with microwaves Ansari, Hussain, et al, 2018;Jha et al, 2009;Waller et al, 2017). NH-IVIGs have shown minor local side effects, tested negative for genotoxicity or mutagenicity, and generated fewer complications than other experimental methods or vasectomies Ansari, Hussain, et al, 2018;Colagross-Schouten et al, 2017;Waller et al, 2016Waller et al, , 2017. In a 2016 survey of men with female sex partners, 41% agreed they would use Vasalgel (King, Kaighobadi, Winecoff, & Lee, 2016).…”