title: Specific deletion of AMP-activated protein kinase (α1AMPK) in mouse Sertoli cells modifies germ cell quality.
abstract: The AMP-activated protein kinase (AMPK) is an important regulator of cellular energy homeostasis which plays a role in fertility. Complete disruption of the AMPK catalytic subunit α1 gene (α1AMPK KO) in male mice results in a decrease in litter size which is associated with the production of altered sperm morphology and motility. Because of the importance of Sertoli cells in the formation of germ cells, we have chosen to selectively disrupt α1AMPK only in the Sertoli cells in mice (Sc-α1AMPK-KO mice). Specific deletion of the α1AMPK gene in Sertoli cells resulted in a 25% reduction in male fertility associated with abnormal spermatozoa with a thin head. No clear alterations in testis morphology or modification in the number of Sertoli cells in vivo were observed, but a dysregulation in energy metabolism in Sertoli cells occurred. We have reported an increase in lactate production, in lipid droplets, and a reduction in ATP production in Sc-α1AMPK-KO Sertoli cells. These perturbations were associated with lower expression of mitochondrial markers (cytochrome c and PGC1-α). In addition another metabolic sensor, the deacetylase SIRT1, had a reduction in expression which is correlated with a decline in deacetylase activity. Finally, expression and localization of junctions forming the blood-testis barrier between Sertoli cells themselves and with germ cells were deregulated in Sc-α1AMPK-KO. In conclusion, these results suggest that dysregulation of the energy sensing machinery exclusively through disruption of α1AMPK in Sertoli cells translates to a reduction in the quality of germ cells and fertility.
authors.affiliation: Unité de Physiologie de la Reproduction et des Comportements, Institut National de la Recherche Agronomique, Centre Val de Loire, UMR85, 37380 Nouzilly, France; School of Women's and Children's Health, Discipline of Obstetrics and Gynaecology, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Bertoldo
authors.affiliation: Unité de Physiologie de la Reproduction et des Comportements, Institut National de la Recherche Agronomique, Centre Val de Loire, UMR85, 37380 Nouzilly, France.
authors.forename: Edith
authors.initials: E
authors.lastname: Guibert
authors.affiliation: Unité de Physiologie de la Reproduction et des Comportements, Institut National de la Recherche Agronomique, Centre Val de Loire, UMR85, 37380 Nouzilly, France.
authors.forename: Melanie
authors.initials: M
authors.lastname: Faure
authors.affiliation: Unité de Physiologie de la Reproduction et des Comportements, Institut National de la Recherche Agronomique, Centre Val de Loire, UMR85, 37380 Nouzilly, France.
authors.forename: Florian
authors.initials: F
authors.lastname: Guillou
authors.affiliation: Unité de Physiologie de la Reproduction et des Comportements, Institut National de la Recherche Agronomique, Centre Val de Loire, UMR85, 37380 Nouzilly, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Ramé
authors.affiliation: INSERM U930, Équipe Neurogénétique et Neurométabolomique, Université François-Rabelais, 37044 Tours, France; Département d'Analyse Chimique Biologique et Médicale, PPF "Analyses des Systèmes Biologiques", Université François-Rabelais, Tours, France.
authors.forename: Lydie
authors.initials: L
authors.lastname: Nadal-Desbarats
authors.affiliation: INSERM, U1016, Institut Cochin, Paris, France; CNRS, UMR8104, Paris, France; Univ Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Foretz
authors.affiliation: INSERM, U1016, Institut Cochin, Paris, France; CNRS, UMR8104, Paris, France; Univ Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Viollet
authors.affiliation: Unité de Physiologie de la Reproduction et des Comportements, Institut National de la Recherche Agronomique, Centre Val de Loire, UMR85, 37380 Nouzilly, France.
authors.forename: Joëlle
authors.initials: J
authors.lastname: Dupont
authors.affiliation: Unité de Physiologie de la Reproduction et des Comportements, Institut National de la Recherche Agronomique, Centre Val de Loire, UMR85, 37380 Nouzilly, France. Electronic address: pascal.froment@tours.inra.fr.
authors.forename: Pascal
authors.initials: P
authors.lastname: Froment
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics* / Q000378:metabolism; D000177:Acrosome / Q000201:enzymology*; D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D005260:Female; D015870:Gene Expression; D007248:Infertility, Male / Q000201:enzymology / Q000235:genetics; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D021381:Protein Transport; D012708:Sertoli Cells / Q000201:enzymology*; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism; D013081:Sperm Motility
chemical_list: D000255:Adenosine Triphosphate; D055372:AMP-Activated Protein Kinases; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1
keywords: AMP-activated protein kinase; Blood testis barrier; Fertility; Metabolism; Sertoli cells; Testis