Regulation of sperm hyperactivation by transporters involved in Na⁺ homeostasis

Abstract

Mammalian sperm have to undergo several physiological and biochemical changes to be fertilization-competent. These changes are collectively called “capacitation”. Capacitated sperm show frantic whiplash-like flagellar movement called “hyperactivation”. Recently, it has been reported that treatments of sperm to enhance hyperactivation improve in vitro fertilization (IVF) and development of the fertilized embryos. This fact indicates that hyperactivation is an attractive target to improve assisted reproductive technologies. However, the detailed mechanisms which regulate hyperactivation have not been fully elucidated. Recently, it was found out that Na⁺ and K⁺ concentration of the oviductal fluid considerably differs from those in the medium used for IVF. Thus, the effect of the Na⁺ and K⁺ concentration on sperm hyperactivation was investigated using hamsters as a model. The results revealed that hamster sperm hyperactivation was suppressed by extracellular Na⁺ via an action of Na⁺/Ca²⁺ exchanger. Moreover, it was shown that the activity of testis specific isoform of Na⁺/K⁺ ATPase (NKA) α subunit, α4, is necessary for the hyperactivation-associated change of the flagellar movement. By contrast, there was no significant effect of raising the K⁺ concentration up to 20 mM on sperm hyperactivation although it significantly depolarized the membrane potential. These results suggests that transporters involved in primary and secondary active transport which regulates cellular Na⁺ homeostasis has a crucial role in the regulation of hyperactivation, and these transporters can be an attractive target for the improvement of assisted reproductive technologies.