Sertoli cell Dicer is essential for spermatogenesis in mice.
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.
Papaioannou
Marilena D
MD
Department of Genetic Medicine and Development, University of Geneva Medical School, 1, rue Michel Servet, 1211 Geneva 4, Switzerland.
Pitetti
Jean-Luc
JL
Ro
Seungil
S
Park
Chanjae
C
Aubry
Florence
F
Schaad
Olivier
O
Vejnar
Charles E
CE
Kühne
Francoise
F
Descombes
Patrick
P
Zdobnov
Evgeny M
EM
McManus
Michael T
MT
Guillou
Florian
F
Harfe
Brian D
BD
Yan
Wei
W
Jégou
Bernard
B
Nef
Serge
S
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
D035683:MicroRNAs; D004722:Endoribonucleases; C509781:Dicer1 protein, mouse; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases