title: Inactivation of AMPKα1 induces asthenozoospermia and alters spermatozoa morphology.
abstract: AMP-activated protein kinase (AMPK), a key regulator of cellular energy homeostasis, is present in metabolic tissues (muscle and liver) and has been identified as a modulator of the female reproductive functions. However, its function in the testis has not yet been clearly defined. We have investigated the potential role of AMPK in male reproduction by using transgenic mice lacking the activity of AMPK catalytic subunit α1 gene [α1AMPK knockout (KO)]. In the testis, the α1AMPK subunit is expressed in germ cells and also in somatic cells (Sertoli and Leydig cells). α1AMPK KO male mice show a decrease in fertility, despite no clear alteration in the testis morphology or sperm production. However, in α1AMPK(-/-) mice, we demonstrate that spermatozoa have structural abnormalities and are less motile than in control mice. These spermatozoa alterations are associated with a 50% decrease in mitochondrial activity, a 60% decrease in basal oxygen consumption, and morphological defects. The α1AMPK KO male mice had high androgen levels associated with a 5- and 3-fold increase in intratesticular cholesterol and testosterone concentrations, respectively. High concentrations of proteins involved in steroid production (3β-hydroxysteroid dehydrogenase, cytochrome steroid 17 alpha-hydroxylase/17,20 lysate, and steroidogenic acute regulatory protein) were also detected in α1AMPK(-/-) testes. In the pituitary, the LH and FSH concentrations tended to be lower in α1AMPK(-/-) male mice, probably due to the negative feedback of the high testosterone levels. These results suggest that total α1AMPK deficiency in male mice affects androgen production and quality of spermatozoa, leading to a decrease in fertility.
authors.affiliation: Unité Mixte de Recherche (UMR) 6175, Physiologie de la Reproduction et des Comportements (Institut National dela Recherche Agronomique/Centre National dela Recherche Scientifique/Université Tours/Haras Nationaux), 37380 Nouzilly, France.
authors.forename: Pauline
authors.initials: P
authors.lastname: Tartarin
authors.forename: Edith
authors.initials: E
authors.lastname: Guibert
authors.forename: Aminata
authors.initials: A
authors.lastname: Touré
authors.forename: Claire
authors.initials: C
authors.lastname: Ouiste
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Leclerc
authors.forename: Nieves
authors.initials: N
authors.lastname: Sanz
authors.forename: Sylvain
authors.initials: S
authors.lastname: Brière
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Dacheux
authors.forename: Bernadette
authors.initials: B
authors.lastname: Delaleu
authors.forename: Judith R
authors.initials: JR
authors.lastname: McNeilly
authors.forename: Alan S
authors.initials: AS
authors.lastname: McNeilly
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Brillard
authors.forename: Joëlle
authors.initials: J
authors.lastname: Dupont
authors.forename: Marc
authors.initials: M
authors.lastname: Foretz
authors.forename: Benoit
authors.initials: B
authors.lastname: Viollet
authors.forename: Pascal
authors.initials: P
authors.lastname: Froment
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000502:physiology*; D000818:Animals; D017209:Apoptosis; D053627:Asthenozoospermia / Q000378:metabolism*; D004734:Energy Metabolism; D005260:Female; D005298:Fertility; D000071518:Liver X Receptors; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission / Q000379:methods; D008954:Models, Biological; D057093:Orphan Nuclear Receptors / Q000378:metabolism; D010053:Ovary / Q000502:physiology; D010101:Oxygen Consumption; D013094:Spermatozoa / Q000378:metabolism* / Q000502:physiology; D013737:Testis / Q000378:metabolism; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; C548179:Prkaa1 protein, mouse; D055372:AMP-Activated Protein Kinases; D001616:beta-Galactosidase