title: Age-dependent loss of sperm production in mice via impaired lysophosphatidic acid signaling.
abstract: Approximately half of all infertility cases can be attributed to male reproductive dysfunction for which low sperm count is a major contributing factor. The current study identified receptor-mediated lysophosphatidic acid (LPA) signaling as a new molecular component influencing male fertility. LPA is a small signaling phospholipid, the effects of which are mediated through at least five G protein-coupled receptors, named LPA 1-5. LPA1/2/3, but not LPA4/5, show high expression in mouse testis. Mice deficient in LPA1/2/3 showed a testosterone-independent reduction of mating activity and sperm production, with an increased prevalence of azoospermia in aging animals. A significant increase of germ cell apoptosis also was observed in testes. Germ cell apoptosis led to a reduction in germ cell proliferation. These data demonstrate a novel in vivo function for LPA signaling as a germ cell survival factor during spermatogenesis.
authors.affiliation: Department of Molecular Biology, The Helen L. Dorris Child and Adolescent Neuropsychiatric Disorder Institute, The Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Ye
authors.forename: Michael K
authors.initials: MK
authors.lastname: Skinner
authors.forename: Grace
authors.initials: G
authors.lastname: Kennedy
authors.forename: Jerold
authors.initials: J
authors.lastname: Chun
mesh_terms: D000367:Age Factors; D000818:Animals; D049109:Cell Proliferation; D005260:Female; D008246:Lysophospholipids / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010766:Phosphorylation; D049368:Receptors, Lysophosphatidic Acid / Q000235:genetics / Q000378:metabolism; D012726:Sexual Behavior, Animal / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics* / Q000502:physiology; D013076:Sperm Count; D013091:Spermatogenesis / Q000235:genetics* / Q000502:physiology; D013094:Spermatozoa / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D013737:Testis / Q000166:cytology / Q000378:metabolism; D013739:Testosterone / Q000097:blood
chemical_list: D008246:Lysophospholipids; D049368:Receptors, Lysophosphatidic Acid; D013739:Testosterone; D048052:Mitogen-Activated Protein Kinase 3; C032881:lysophosphatidic acid