Dicer1 Depletion in Male Germ Cells Leads to Infertility Due to Cumulative Meiotic and Spermiogenic Defects 英文参考文献.docVIP

Dicer1DepletioninMaleGermCellsLeadstoInfertility DuetoCumulativeMeioticandSpermiogenicDefects YannickRomero1,OliverMeikar2,MarilenaD.Papaioannou1,Be′atriceConne1,CorinneGrey3 ,Manuela Weier4,Franc?ois Pralong5,BernardDeMassy3,HenrikKaessmann4,Jean-DominiqueVassalli1 ,Noora Kotaja2,SergeNef1* 1 Department of Genetic Medicine and Development, University of Geneva Medical School, University of Geneva, Geneva, Switzerland, 2 Department of Physiology, Institute of Biomedicine, University of Turku, Turku, Finland, 3 Institut de Ge′ne′tique Humaine, IGH - CNRS, Montpellier, France, 4 Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland,5 Department of Internal Medicine, University Hospital, Lausanne, Switzerland Abstract Background: Spermatogenesis is a complex biological process that requires a highly specialized control of gene expression. In the past decade, small non-coding RNAs have emerged as critical regulators of gene expression both at the transcriptional and post-transcriptional level. DICER1, an RNAse III endonuclease, is essential for the biogenesis of several classes of small RNAs, including microRNAs (miRNAs) and endogenous small interfering RNAs (endo-siRNAs), but is also critical for the degradation of toxic transposable elements. In this study, we investigated to which extent DICER1 is required for germ cell development and the progress of spermatogenesis in mice. PrincipalFindings: We show that the selective ablation ofDicer1 at the early onset of male germ cell development leads to infertility, due to multiple cumulative defects at the meiotic and post-meiotic stages culminating with the absence of functional spermatozoa. Alterations were observed in the first spermatogenic wave and include delayed progression of spermatocytes to prophase I and increased apoptosis, resulting in a