Mammalian sperm including human have to undergo several physiological and biochemical changes, collectively called capacitation, to be fertilization-competent. Capacitated sperm show specialized vigorous motility called hyperactivation. Hyperactivation is necessary to progress in the viscous oviductal environment.
We found that the fluid of oviduct, where fertilization occurs, contains higher concentration of Na⁺ than in the media used for in vitro fertilization (IVF). Therefore, we first investigated if this difference in the concentration of Na⁺ affects hyperactivation or not. We found that increase in the Na⁺ concentration delays the hyperactivation by lowering intracellular Ca²⁺ levels ([Ca²⁺]_i). The Na⁺/Ca²⁺ exchanger (NCX)-specific inhibitor SEA0400 increased [Ca²⁺]_i, and canceled the delay of hyperactivation by Na⁺. These results suggest that NCX is involved in the regulation of hyperactivation. Next, we searched for the NCX isoforms expressed in hamster sperm, and found that NCX1 mRNA and protein are expressed in the hamster testis and sperm. Lastly, we tried to detect NCX1 activity by measuring Na⁺-dependent Ca²⁺ influx by Fura2. The Na⁺-dependent Ca²⁺ influx was detected in hamster sperm, and was inhibited by SEA0400 at NCX1 specific concentration. Moreover, NCX1 activity was declined in the capacitated sperm. These results showed that NCX1 functions as a “brake” of hyperactivation in the hamster sperm, and its downregulation triggers hyperactivation. An inhibitor of NCX1 is a possible candidate drug to facilitate IVF.