Sulfhydryl Groups on the Spermatozoa Membrane. A Study with a New Fluorescent Probe for SH Group1

After leaving the testis, sperm have not yet acquired the ability to move progressively and are unable to fertilize oocytes. To become fertilization-competent they must go through an epididymal maturation process in the male, and capacitation in the female tract. Epididymal maturation can be defined as those changes occurring to sperm in the epididymis that render the sperm the ability to capacitate in the female tract. As part of this process, sperm cells undergo a series of biochemical and physiological changes that require incorporation of new molecules derived from the epididymal epithelium, as well as post-translational modifications of endogenous proteins synthesized during spermiogenesis in the testis. This review will focus on epididymal maturation events, with emphasis in recent advances in the understanding of the molecular basis of this process.

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“…1983, Saowaros et al . 1979) or sperm membrane proteins (Mercado et al . 1976) during epididymal transit.…”

Section: Sperm Changes Occurring During Epididymal Transitmentioning

confidence: 99%

Molecular changes and signaling events occurring in spermatozoa during epididymal maturation

2017

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“…Accordingly, a modest 30% reduction in fertility rate of rabbits has been reported with 25 mg N-9 in OTC vaginal cream formulation [38]. It is also pertinent to note that rabbit sperm have fewer thiols than human sperm [8], which could further weaken the sperm-paralyzing effects of –SH binding agents like PPC in rabbits. Yet, PPC exhibited an apparently higher contraceptive potential than the surfactant nonoxynol-9 under experimental conditions.…”

Section: Discussionmentioning

confidence: 99%

“…According to an estimate, human sperm contain >55 nmoles of ‘reactive’ thiols per 10 8 cells which are ∼30 times more than those on erythrocytes [8]. The significance of thiols in sperm cell motility/function is evident from the fact that asthenozoospermic infertile men have significantly less thiols on sperm than normozoospermic men [9].…”

Section: Introductionmentioning

confidence: 99%

Designed Chemical Intervention with Thiols for Prophylactic Contraception

et al. 2013

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Unlike somatic cells, sperm have several-fold more available-thiols that are susceptible to redox-active agents. The present study explains the mechanism behind the instant sperm-immobilizing and trichomonacidal activities of pyrrolidinium pyrrolidine-1-carbodithioate (PPC), a novel thiol agent rationally created for prophylactic contraception by minor chemical modifications of some known thiol drugs. PPC, and its three derivatives (with potential active-site blocked by alkylation), were synthesized and evaluated against live human sperm and metronidazole-susceptible and resistant Trichomonas vaginalis, in vitro. Sperm hexokinase activity was evaluated by coupled enzyme assay. PPC irreversibly immobilized 100% human sperm in ∼30 seconds and totally eliminated Trichomonas vaginalis more efficiently than nonoxynol-9 and metronidazole. It significantly inhibited (P<0.001) thiol-sensitive sperm hexokinase. However, the molecule completely lost all its biological activities once its thiol group was blocked by alkylation. PPC was subsequently formulated into a mucoadhesive vaginal film using GRaS excipients and evaluated for spermicidal and microbicidal activities (in vitro), and contraceptive efficacy in rabbits. PPC remained fully active in quick-dissolving, mucoadhesive vaginal-film formulation, and these PPC-films significantly reduced pregnancy and fertility rates in rabbits. The films released ∼90% of PPC in simulated vaginal fluid (pH 4.2) at 37°C in 5 minutes, in vitro. We have thus discovered a common target (reactive thiols) on chiefly-anaerobic, redox-sensitive cells like sperm and Trichomonas, which is susceptible to designed chemical interference for prophylactic contraception. The active thiol in PPC inactivates sperm and Trichomonas via interference with crucial sulfhydryl-disulfide based reactions, e.g. hexokinase activation in human sperm. In comparison to non-specific surfactant action of OTC spermicide nonoxynol-9, the action of thiol-active PPC is apparently much more specific, potent and safe. PPC presents a proof-of-concept for prophylactic contraception via manipulation of thiols in vagina for selective targeting of sperm and Trichomonas, and qualifies as a promising lead for the development of dually protective vaginal-contraceptive.

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“…Various maleimides have been reported to have inhibitory effects on human and rabbit spermatozoa, possibly by a mechanism involving membrane sulphydryl groups Mercado, Carvajal, Reyes & Rosado, 1976;Reyes, Mercado, Goicoechea & Rosado, 1976).…”

Section: Discussionmentioning

confidence: 99%

Effect of antidepressant drugs on the in-vitro eggpenetrating ability of golden hamster epididymal spermatozoa

Stein¹,

Schnieden²

1983

Reproduction

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Tricyclic antidepressants appeared to be without effect, except for desipramine which significantly decreased whiplash motility after spermatozoa were added to eggs, and clomipramine which decreased motility and whiplash motility in epididymal sperm suspensions after pretreatment of males. Mianserin and viloxazine were also without effect, but nomifensine significantly decreased sperm motility and whiplash motility and inhibited egg penetration almost completely. After 3 h preincubation with 0\m=.\75mmol nomifensine hydrogen maleate/l, 2/181 and 0/256 eggs were penetrated in two separate series of experiments. Control groups in these series gave medians of 90\p=n-\100%penetration by 4\m=.\5\p=n-\5\m=.\5h after spermatozoa and eggs were mixed. Maleic acid had a similar effect (1/253 eggs penetrated) whilst nomifensine hydrochloride was inactive, suggesting that the effect was due to the maleate moiety of the original nomifensine hydrogen maleate salt used.

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Sulfhydryl Groups on the Spermatozoa Membrane. A Study with a New Fluorescent Probe for SH Group1

Cited by 24 publications

References 28 publications

Molecular changes and signaling events occurring in spermatozoa during epididymal maturation

Molecular changes and signaling events occurring in spermatozoa during epididymal maturation

Designed Chemical Intervention with Thiols for Prophylactic Contraception

Effect of antidepressant drugs on the in-vitro eggpenetrating ability of golden hamster epididymal spermatozoa

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