Plant-derived compounds block sperm tail whipping

When sperm cells go swimming, their tails normally wag symmetrically. But once sperm get near an egg, their tails start whipping forcefully. This extra effort improves the cells’ chance of penetrating the egg’s viscous surroundings to start fertilization. A rush of calcium ions through an ion channel called CatSper triggers this change in tail motion. A study describes how hormones in males and females can regulate the opening of CatSper, as well as reports two plant-derived compounds that inhibit activation of the ion channel and could serve as novel contraceptives (Proc. Natl. Acad. Sci. USA 2017, DOI: 10.1073/pnas.1700367114). Nadja Mannowetz, Melissa R. Miller, and Polina V. Lishko of the University of California, Berkeley, found that both testosterone and hydrocortisone—the pharmaceutical version of the hormone cortisol—inhibit CatSper opening. Relatively high testosterone levels and chronic stress, which increases cortisol levels, are known to lower fertility in women. The team also tested two plant triterpenoids that have anecdotal evidence of impairing fertility: pristimerin, found in a vine used in traditional Chinese medicine, and lupeol, found in mangoes. Both reduced CatSper activation. All these molecules block CatSper activation by inhibiting an enzyme called ABHD2. This enzyme degrades a compound in sperm that turns off CatSper. The researchers next plan to test the contraceptive properties of pristimerin and lupeol in nonhuman primates.