title: Establishment of cell-cell cross talk in the epididymis: control of luminal acidification.
abstract: Male infertility is often caused by sperm that have low motility and  interact poorly with the oocyte. Spermatozoa acquire these crucial functions  in the epididymis. A low luminal bicarbonate  (HCO(3)(-)) concentration and low pH keep sperm  quiescent during their maturation and storage in this organ. This review  describes how epididymal epithelial cells work in a concerted manner, together  with spermatozoa, to establish and maintain this acidic luminal environment.  Clear cells express the proton-pumping ATPase (V-ATPase) in their apical  membrane and actively secrete protons. HCO(3)(-)  induces V-ATPase accumulation in apical microvilli in clear cells via  HCO(3)(-)-sensitive adenylyl cyclase-dependent  cAMP production. HCO(3)(-) is secreted from principal  cells following basolateral stimulation, to transiently "prime"  spermatozoa before ejaculation. Luminal ATP and adenosine also induce V-ATPase  apical accumulation in clear cells via activation of P2 and P1 receptors,  respectively. ATP is released into the lumen from sperm and principal cells  and is then metabolized into adenosine by local nucleotidases. In addition,  the V-ATPase is regulated by luminal angiotensin II via activation of basal  cells, which can extend narrow body projections that cross the tight junction  barrier. Basal cells then secrete nitric oxide, which diffuses out to  stimulate proton secretion in clear cells via activation of the cGMP pathway.  Thus, an elaborate communication network is present between principal cells  and clear cells, and between basal cells and clear cells, to control luminal  acidification. Monitoring and decoding these "intercellular  conversations" will help define pathophysiologic mechanisms underlying  male infertility.
authors: Program in Membrane Biology, MGH Simches Research Center, 185 Cambridge Street, Boston, MA 02114, USA.
authors: Winnie W C
authors: WW
authors: Shum
authors: Ye Chun
authors: YC
authors: Ruan
authors: Nicolas
authors: N
authors: Da Silva
authors: Sylvie
authors: S
authors: Breton
mesh_terms: D000241:Adenosine / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D002450:Cell Communication; D006152:Cyclic GMP / Q000378:metabolism; D004822:Epididymis / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D011983:Receptors, Purinergic / Q000378:metabolism; D013094:Spermatozoa / Q000378:metabolism*; D019108:Tight Junctions / Q000378:metabolism; D025262:Vacuolar Proton-Translocating ATPases / Q000378:metabolism*
chemical_list: D001639:Bicarbonates; D011983:Receptors, Purinergic; D000804:Angiotensin II; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D025262:Vacuolar Proton-Translocating ATPases; D006152:Cyclic GMP; D000241:Adenosine