Papaioannou Marilena D, Pitetti Jean-Luc, Ro Seungil, Park Chanjae, Aubry Florence, Schaad Olivier, Vejnar Charles E, Kühne Francoise, Descombes Patrick, Zdobnov Evgeny M, McManus Michael T, Guillou Florian, Harfe Brian D, Yan Wei, Jégou Bernard, Nef Serge
Department of Genetic Medicine and Development, University of Geneva Medical School, 1, rue Michel Servet, 1211 Geneva 4, Switzerland.
Dev Biol. 2009 Feb 1;326(1):250-9. doi: 10.1016/j.ydbio.2008.11.011. Epub 2008 Nov 28.
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.
精子发生需要完整且功能完全正常的支持细胞。在此，我们研究了Dicer（一种参与微小RNA和小干扰RNA生物合成的核糖核酸酶III内切酶）在小鼠支持细胞功能中的作用。我们发现，支持细胞中Dicer的选择性缺失会导致不育，原因是精子完全缺失以及睾丸进行性退化。最早的形态学改变在出生后第5天就已出现，这与青春期前精子发生波的严重受损相关，这是由于支持细胞成熟缺陷以及无法正常支持减数分裂和精子形成所致。重要的是，我们发现几个已知对支持细胞功能至关重要的关键基因在支持细胞中缺乏Dicer的新生睾丸中显著下调。总体而言，我们的结果揭示了Dicer依赖性途径在哺乳动物生殖功能中发挥的新的重要作用，从而为深入了解人类不育症开辟了新的途径。
