PLoS One; co-auth H. Kaessmann

PLoS One. 2011;6(10):e25241. Epub 2011 Oct 5.

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

Romero Y, Meikar O, Papaioannou MD, Conne B, Grey C, Weier M, Pralong F, De Massy
B, Kaessmann H, Vassalli JD, Kotaja N, Nef S.

Department of Genetic Medicine and Development, University of Geneva Medical
School, University of Geneva, Geneva, Switzerland.

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.

PMID: 21998645 [PubMed - in process]