Contraceptive efficacy of antimicrobial peptide Nisin: in vitro and in vivo studies

Sexually transmitted infections and unplanned pregnancies present a great risk to the reproductive health of women. Therefore, female-controlled vaginal products directed toward disease prevention and contraception are needed urgently. In the present study, efforts were made to evaluate the contraceptive potential of Nisin. The effect of Nisin on sperm motility was assessed under in vitro and in vivo conditions. The results showed that sperm motility was completely inhibited with Nisin. The minimum effective concentration of Nisin required to immobilize sperm (80-100 x 10(6)) in vitro within 20 s was found to be 50 mug in rat, 200 mug in rabbit and 300-400 mug in monkey and human. The effect on sperm motility was observed to be dose- and time-dependent. Intravaginal administration of Nisin (200 mug) before mating during proestrus-estrous transition phase caused complete arrest of sperm motility and blockage of conception. Subacute toxicity studies in rats indicated that, repetitive intravaginal application of Nisin at the dose of 200 mug for 14 consecutive days induced no abnormalities either in the length of estrous cycle or in the morphology of vaginal epithelial cells. No histopathological abnormalities in vaginal tissue or any change in blood and serum biochemical profiles were observed. Furthermore, no adverse effects were observed on subsequent reproductive performance, neonate survival and development of pups. It is suggested that Nisin, with its antibacterial and spermicidal activities, could be developed as a potent vaginal contraceptive for future use in humans. (C) 2004 Elsevier Inc. All rights reserved.