Dicer1 depletion in male germ cells leads to infertility due to cumulative meiotic and spermiogenic defects

Autor: Manuela Weier, Serge Nef, Jean-Dominique Vassalli, Noora Kotaja, François P. Pralong, Henrik Kaessmann, Béatrice Conne, Bernard de Massy, Marilena D. Papaioannou, Corinne Grey, Oliver Meikar, Yannick Romero
Přispěvatelé: Université de Genève (UNIGE), Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université de Lausanne (UNIL), University of Turku
Jazyk: angličtina
Rok vydání: 2011
Předmět:
Ribonuclease III
Male
Organ Size/genetics
Anatomy and Physiology
Ribonuclease III/deficiency/genetics
lcsh:Medicine
Gene Expression
Apoptosis
DEAD-box RNA Helicases
Mice
0302 clinical medicine
Spermatocytes
Reproductive Physiology
Apoptosis/genetics
Gene expression
Molecular Cell Biology
ddc:576.5
lcsh:Science
[SDV.BDD.GAM]Life Sciences [q-bio]/Development Biology/Gametogenesis
Genetics
0303 health sciences
030219 obstetrics & reproductive medicine
Multidisciplinary
Cell Death
Infertility
Male/genetics/pathology
Sperm Count
Cell Differentiation
Organ Size
Spermatozoa/metabolism/pathology
Seminiferous Tubules
Spermatocytes/metabolism/pathology
Spermatozoa
DNA Transposable Elements/genetics
Meiosis
medicine.anatomical_structure
Germ cell
Cell Division
Research Article
Transgene
Mitosis
Mice
Transgenic
Biology
03 medical and health sciences
[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Genomics [q-bio.GN]
microRNA
medicine
Gene silencing
Animals
Gene Silencing
Spermatogenesis
Infertility
Male
030304 developmental biology
Spermatogenesis/genetics
lcsh:R
Reproductive System
MicroRNAs
MicroRNAs/genetics
Meiosis/genetics
Seminiferous Tubules/metabolism/pathology
Fertilization
biology.protein
DNA Transposable Elements
lcsh:Q
Gene Function
DEAD-box RNA Helicases/deficiency/genetics
Biogenesis
Gene Deletion
Developmental Biology
Zdroj: PLoS One, vol. 6, no. 10, pp. e25241
PLOS ONE, Vol. 6, No 10 (2011) P. e25241
PLoS ONE
PLoS ONE, Public Library of Science, 2011, 6 (10), pp.E25241. ⟨10.1371/journal.pone.0025241⟩
PLoS ONE, Vol 6, Iss 10, p e25241 (2011)
PloS one
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0025241⟩
Popis: International audience; 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.Principal Findings: We show that the selective ablation of Dicer1 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 reduced number of round spermatids. The transition from round to mature spermatozoa was also severely affected, since the few spermatozoa formed in mutant animals were immobile and misshapen, exhibiting morphological defects of the head and flagellum. We also found evidence that the expression of transposable elements of the SINE family is up-regulated in Dicer1-depleted spermatocytes.Conclusions/Significance: Our findings indicate that DICER1 is dispensable for spermatogonial stem cell renewal and mitotic proliferation, but is required for germ cell differentiation through the meiotic and haploid phases of spermatogenesis.
Databáze: OpenAIRE
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