title: Sertoli cell Dicer is essential for spermatogenesis in mice.
abstract: Spermatogenesis requires intact, fully competent Sertoli cells. Here, we investigate the functions of Dicer, an RNaseIII endonuclease required for microRNA and small interfering RNA biogenesis, in mouse Sertoli cell function. We show that selective ablation of Dicer in Sertoli cells leads to infertility due to complete absence of spermatozoa and progressive testicular degeneration. The first morphological alterations appear already at postnatal day 5 and correlate with a severe impairment of the prepubertal spermatogenic wave, due to defective Sertoli cell maturation and incapacity to properly support meiosis and spermiogenesis. Importantly, we find several key genes known to be essential for Sertoli cell function to be significantly down-regulated in neonatal testes lacking Dicer in Sertoli cells. Overall, our results reveal novel essential roles played by the Dicer-dependent pathway in mammalian reproductive function, and thus pave the way for new insights into human infertility.
authors.affiliation: Department of Genetic Medicine and Development, University of Geneva Medical School, 1, rue Michel Servet, 1211 Geneva 4, Switzerland.
authors.forename: Marilena D
authors.initials: MD
authors.lastname: Papaioannou
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Pitetti
authors.forename: Seungil
authors.initials: S
authors.lastname: Ro
authors.forename: Chanjae
authors.initials: C
authors.lastname: Park
authors.forename: Florence
authors.initials: F
authors.lastname: Aubry
authors.forename: Olivier
authors.initials: O
authors.lastname: Schaad
authors.forename: Charles E
authors.initials: CE
authors.lastname: Vejnar
authors.forename: Francoise
authors.initials: F
authors.lastname: Kühne
authors.forename: Patrick
authors.initials: P
authors.lastname: Descombes
authors.forename: Evgeny M
authors.initials: EM
authors.lastname: Zdobnov
authors.forename: Michael T
authors.initials: MT
authors.lastname: McManus
authors.forename: Florian
authors.initials: F
authors.lastname: Guillou
authors.forename: Brian D
authors.initials: BD
authors.lastname: Harfe
authors.forename: Wei
authors.initials: W
authors.lastname: Yan
authors.forename: Bernard
authors.initials: B
authors.lastname: Jégou
authors.forename: Serge
authors.initials: S
authors.lastname: Nef
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D053487:DEAD-box RNA Helicases / Q000502:physiology*; D015536:Down-Regulation / Q000502:physiology; D004722:Endoribonucleases / Q000502:physiology*; D007248:Infertility, Male / Q000235:genetics / Q000378:metabolism; D008297:Male; D008540:Meiosis / Q000502:physiology; D051379:Mice; D008817:Mice, Mutant Strains; D035683:MicroRNAs / Q000378:metabolism; D043244:Ribonuclease III; D012708:Sertoli Cells / Q000378:metabolism*; D013091:Spermatogenesis / Q000502:physiology*; D013737:Testis / Q000002:abnormalities / Q000254:growth & development* / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D004722:Endoribonucleases; C509781:Dicer1 protein, mouse; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases