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Vaginal Contraceptive Activity of a Chelated Vanadocene

Vaginal Contraceptive Activity of a Chelated Vanadocene

Osmond J D'Cruz, Fatih M Uckun

Contraception. 2005 Aug;72(2):146-56.

PMID: 16022855

Abstract:

Bis(cyclopentadienyl) complexes of vanadium (IV) or vanadocenes are rapid and potent inhibitors of human sperm motility with potential as a new class of contraceptive agents. This study sought to determine the vaginal contraceptive activity of vanadocene dithiocarbamate (VDDTC), a stable vanadocene (IV)-chelated complex, using the standard rabbit model as well as the domestic pig as a physiologically relevant animal model for contraception. In experiment I, ovulating New Zealand White does in subgroups of eight were artificially inseminated (AI) with semen mixed with VDDTC (0.01-1 mM) or vehicle. In experiment II, ovulating does in subgroups of 18 were AI at 5 and 60 min after intravaginal application of a gel with and without 0.1% VDDTC or 2% nonoxynol-9 (N-9) (Gynol II, Ortho Pharmaceutical, Raritan, NJ), and allowed to complete term pregnancy. In experiment III, seven sexually mature Duroc gilts in standing estrus were AI with and without intravaginal application of 0.1% VDDTC gel microemulsion. Exposure of rabbit semen to VDDTC at the time of artificial insemination resulted in a dose-dependent reduction in fertility. Exposure of semen to 1 mM VDDTC led to complete inhibition of fertility as assessed by the number of embryos (control 49/94 vs. VDDTC-treated 0/117, p<.0001) or the percent embryos (52% vs. 0%, respectively) based on number of embryos to corpora lutea. Intravaginal administration of 0.1% VDDTC gel microemulsion or Gynol II prior to artificial insemination significantly inhibited term pregnancy rates (88% and 62% inhibition, respectively) when compared to control gel alone. Vanadocene dithiocarbamate gel microemulsion provided 80% inhibition of fertility even when insemination was delayed until 60 min after intravaginal application of VDDTC gel microemulsion. Rabbits that delivered litters despite intravaginal exposure of semen to VDDTC via gel microemulsion had healthy offsprings with no apparent perinatal repercussions. In domestic pigs, intravaginal applications of 0.1% VDDTC gel microemulsion prior to artificial insemination led to complete inhibition of fertility as assessed by the number of embryos (control 29/52 vs. VDDTC-treated 0/44, p<.0001) or the percent embryos (56% vs. 0%, respectively) based on the number of embryos to corpora lutea. These results suggest that VDDTC is a potent contraceptive agent in vivo. Intravaginal use of VDDTC via a gel microemulsion has clinical potential as a safe alternative to currently used detergent-type contraceptives.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1277470	Bis(cyclopentadienyl)vanadium(II)		1277-47-0	Price

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