Abstract
The concurrent increases in global population and sexually transmitted infection (STI) demand a search for agents with dual spermicidal and microbicidal properties for topical vaginal application. Previous attempts to develop the surfactant spermicide, nonoxynol-9 (N-9), into a vaginal microbicide were unsuccessful largely due to its inefficiency to kill microbes. Furthermore, N-9 causes damage to the vaginal epithelium, thus accelerating microbes to enter the women’s body. For this reason, antimicrobial peptides (AMPs), naturally secreted by all forms of life as part of innate immunity, deserve evaluation for their potential spermicidal effects. To date, twelve spermicidal AMPs have been described including LL-37, magainin 2 and nisin A. Human cathelicidin LL-37 is the most promising spermicidal AMP to be further developed for vaginal use for the following reasons. First, it is a human AMP naturally produced in the vagina after intercourse. Second, LL-37 exerts microbicidal effects to numerous microbes including those that cause STI. Third, its cytotoxicity is selective to sperm and not to the female reproductive tract. Furthermore, the spermicidal effects of LL-37 have been demonstrated in vivo in mice. Therefore, the availability of LL-37 as a vaginal spermicide/microbicide will empower women for self-protection against unwanted pregnancies and STI.
Highlights
‚ Gardnerella vaginalis ‚ Prevotella spp. ‚ Porphyromonas spp. ‚ Bacteroides spp. ‚ Peptostreptococcus spp. ‚ Mycoplasma hominis ‚ Ureaplasma urealyticum ‚ Mobiluncus spp
The development of N-9 into a spermicide over 50 years ago did not take into account the physiology of sperm function, the knowledge of which has been slowly unfolding over the past decades
Upon exposure to stimulators such as zona pellucida (ZP) glycoproteins and progesterone, calcium is rapidly transported into sperm, and the acrosome reaction is initiated with the multi-site fusion between the sperm anterior head plasma membrane and the outer acrosomal membrane
Summary
As the world population continues to grow at an exponential rate, so does the need for novel contraceptives. Progestin thickens the cervical mucus, impeding sperm from swimming into the uterus and oviduct These features empower women to protect themselves from unwanted pregnancies and have become the most widely used form of contraception. These sex steroid based pills are not without risks, as estrogen and progestin are involved in other physiological processes outside of ovulation and pregnancy. Bacteria, yeasts and protozoa cause sexually transmitted infection (Table 1) via this route Physical barriers such as male and female condoms prevent transmission of potential pathogens between both sexes. Details of the current knowledge on sperm physiology/biochemistry are given for consideration of the development of the generation of vaginal contraceptive/microbicide compounds
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