title: Anion exchanger 2 is essential for spermiogenesis in mice.
abstract: Na+-independent anion exchangers (AE) mediate electroneutral exchange of Cl- for HCO3- ions across cell membranes, being involved in intracellular pH and cell volume regulation and in transepithelial hydroionic fluxes. Bicarbonate activation of adenylyl cyclase is known to be necessary for sperm motility and sperm capacitation, and a few studies have suggested a possible role of AE carriers in reproduction. Among the four AE genes identified in mammals thus far, only Ae2 (Slc4a2) has been determined to be expressed in the male reproductive system, especially in developing spermatozoa and in epididymal epithelium. Most AE genes drive alternative transcription, which in mouse Ae2 results in several Ae2 isoforms. Here, we generated mice carrying a targeted disruption of Ae2 that prevents the expression of the three AE2 isoforms (Ae2a, Ae2b1, and Ae2b2) normally found in mouse testes. Male Ae2-/- mice (but not female Ae2-/- mice) are infertile. Histopathological analysis of Ae2-/- testes shows an interruption of spermiogenesis, with only a few late spermatids and a complete absence of spermatozoa in the seminiferous tubules. The number of apoptotic bodies is increased in the seminiferous tubules and in the epididymis, which also shows squamous metaplasia of the epididymal epithelium. Our findings reveal an essential role of Ae2 in mouse spermiogenesis and stress the recently postulated involvement of bicarbonate in germ-cell differentiation through the bicarbonate-sensitive soluble-adenylyl-cyclase pathway.
authors.affiliation: Division of Hepatology and Gene Therapy, University Hospital/School of Medicine, Fundación para la Investigación Medica Aplicada, University of Navarra, E-31008 Pamplona, Spain. jfmedina@unav.es
authors.forename: Juan F
authors.initials: JF
authors.lastname: Medina
authors.forename: Sergio
authors.initials: S
authors.lastname: Recalde
authors.forename: Jesús
authors.initials: J
authors.lastname: Prieto
authors.forename: Jon
authors.initials: J
authors.lastname: Lecanda
authors.forename: Elena
authors.initials: E
authors.lastname: Saez
authors.forename: Colin D
authors.initials: CD
authors.lastname: Funk
authors.forename: Paola
authors.initials: P
authors.lastname: Vecino
authors.forename: Marian A
authors.initials: MA
authors.lastname: van Roon
authors.forename: Roelof
authors.initials: R
authors.lastname: Ottenhoff
authors.forename: Piter J
authors.initials: PJ
authors.lastname: Bosma
authors.forename: Conny T
authors.initials: CT
authors.lastname: Bakker
authors.forename: Ronald P J Oude
authors.initials: RP
authors.lastname: Elferink
mesh_terms: D000818:Animals; D027321:Anion Transport Proteins; D017920:Antiporters; D027963:Chloride-Bicarbonate Antiporters; D004822:Epididymis / Q000166:cytology / Q000502:physiology; D004847:Epithelial Cells / Q000502:physiology; D017353:Gene Deletion; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D012016:Reference Values; D064606:SLC4A Proteins; D013076:Sperm Count; D013091:Spermatogenesis / Q000502:physiology*; D013094:Spermatozoa / Q000002:abnormalities / Q000166:cytology / Q000502:physiology*; D013737:Testis / Q000033:anatomy & histology
chemical_list: D027321:Anion Transport Proteins; D017920:Antiporters; D027963:Chloride-Bicarbonate Antiporters; D008565:Membrane Proteins; D064606:SLC4A Proteins; C579495:Slc4a2 protein, mouse