NHE8 plays important roles in male fertility

Abstract

Testes have the dual function of producing sperm and testosterone. Multiple sodium/hydrogen exchanger (NHE) isoforms are expressed in the testes. NHE2 and NHE3 are expressed on the apical membrane of epithelial cells in the efferent and epididymal ducts. The testes of mice lacking NHE3 function have increased fluid volume, which leads to diminished sperm concentration and subfertility. NHE10 is an NHE isoform found in the spermatozoa. Mice lacking of NHE10 are completely infertile due to severely diminished sperm motility. NHE8 is the newest member of the NHE family. Male mice lacking NHE8 are infertile. The overall histological structure in the testes is similar between NHE8KO mice and wild type mice. NHE8KO mice have smaller testis and severely reduced serum testosterone level. NHE8KO male mice have very low number of spermatozoa in the epididymis and virtually none reached the vas deferens. PCR and Western blotting revealed that NHE8 expression is highly abundant in the testes. Immunohistochemistry located NHE8 protein in Leydig cells and in epididymal duct cells. High expression of NHE8 in the Leydig cells and low serum testosterone level in NHE8KO males strongly suggest a critical role for this new NHE isoform in Leydig cell physiology. This study is supported by NIH grant R01DK073638.