Journal
DEVELOPMENTAL BIOLOGY
Volume 326, Issue 1, Pages 250-259Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ydbio.2008.11.011
Keywords
Dicer; MicroRNAs; Sertoli cells; Germ cells; Testis; Spermatogenesis
Categories
Funding
- Swiss National Science Foundation [3100A0-119862]
- Dr. Max Cloetta Foundation
- Societe Academique de Geneve
- National Institute of Health [HD048855, HD050281]
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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. (C) 2008 Elsevier Inc. All rights reserved.
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