Effects of gossypol on the motility of mammalian sperm

The effects of the male contraceptive gossypol on the motility of mammalian spermatozoa are reviewed. The role of sperm motility in the processes of fertilization and the effect of the drug on these processes determine its effectiveness as a contraceptive. The promising male contraceptive potential of gossypol is discussed in the context of the serious adverse effects of the agent. A survey of the research on gossypol, the lipophilic agent derived from cotton seed already being used as male oral contraceptive in China and Brazil, leaves many questions unanswered as to its mode of action and safety. Gossypol is a polyphenolic dialdehyde, occurring in 2 racemic isomers with different biological activities. It is soluble in lipids, binds to membranes, inhibits several enzymes including arachidonate lipoxygenases, and is an antioxidant. It has been used traditionally to treat bronchitis and to induce abortion and menses, but was only recognized as a male antifertility agent in the 1970s. It is spermicidal, it inhibits sperm motility, and causes azoospermia, at different doses and with marked species variability. There is evidence from China for regional variation in effect, possibly related to genetic factors, or even more likely due to dietary intake. Whether infertility induced by gossypol is reversible is in dispute. The most common toxic side effect is hypokalemia, which is severe enough to cause temporary paralysis in 1% of 8806 volunteers in a study conducted in China. Whether potassium loss can be reversed by supplementation, or by taking potassium-sparing diuretics, has been questioned. Similarly, the extent and permanence of renal damage presumed responsible for potassium loss is uncertain. A suitable animal model for studies on gossypol, either in vivo or in vitro, is unavailable. Studies on the mechanism of action of gossypol suggest structural alterations of cell membranes, inhibition of enzymes and energy metabolism may be affected, but this type of work needs to be refined to pinpoint the site of action.