Role of Na⁺/H⁺ exchanger 3 in the acidification of the male reproductive tract and male fertility

Male fertility is a complex process that is dependent on sex hormones and the normal function of the reproductive organs. Defects of these organs result in abnormal sperm production and function, which, in turn, lead to infertility. Spermatozoa released from the testis are unable to move and fertilize with eggs. These features, known as sperm maturation, are acquired during their transit through the epididymis. Among several processes that take place in the epididymis, absorption and acidification of the luminal fluid are essential for sperm maturation, sperm storage and fertility. Currently, the mechanism by which acidification occurs in the epididymis is still not fully understood. The epididymis is fully equipped with the proteins required for acid/base transport, such as Na⁺/H⁺ exchanger 3 (NHE3, SLC9A3), vacuolar-type adenosine triphosphatase (V-ATPase) and various isoforms of enzyme carbonic anhydrase (CA). Most studies, so far, have focused on the role of V-ATPase on H⁺ secretion and acidification of the epididymis. The involvement of NHE3 in creating the acidic environment of the epididymal spermatozoa receives little attention. This review presents evidence for and discusses the role of NHE3 in the acidification of the male reproductive tract and its requirement for male fertility.