Sertoli cell Dicer is essential for spermatogenesis in mice

Abstract

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.

A multi-faceted approach to understanding male infertility: gene mutations, molecular defects and assisted reproductive techniques (ART)

“…For instance, knockout of Dicer1 in mice Sertoli cells or male germ cells leads to infertility due to impaired spermatogenesis, progressive testicular degeneration and both meiotic and spermiogenic defects [193]. Papaioannou et al, [194] also reported that ablation of Dicer1 in Sertoli cells leads to infertility due to the complete absence of functional spermatozoa and progressive testicular degeneration. Another study indicated that Dicer1 is unnecessary for spermatogonial stem cell renewal and mitotic proliferation, but is required for germ cell differentiation through the meiotic and haploid phases of spermatogenesis.…”

Cyclin T2: A novel miR‐15a target gene involved in early spermatogenesis

“…Dead end 1 (Dnd1), an evolutionarily conserved RNA binding protein, was shown to be essential for primordial germ cell development and spermatogenesis in zebrafish and mouse by protecting certain mRNAs from miRNA-mediated repression [10][11][12][13], and was newly reported to regulate mitotic arrest and differentiation in male germ cells [14]. Additionally, Dicer, a requisite enzyme for miRNA processing, was proved to be crucial for both the male germline and Sertoli cells in spermatogenesis [15][16][17][18].…”

Cell‐specific ablation in the testis: what have we learned?

“…It has been shown that Sertoli cells will undergo apoptosis postnatally in mice lacking Sertoli cell expression of Dicer, which is required for micro RNA and small interfering RNA biogenesis (Papaioannou et al ., 2009; Kim et al ., 2010). Sertoli cell apoptosis starts at about postnatal day 3 in these animals although some Sertoli cells survive into adulthood.…”

“…Sertoli cell apoptosis starts at about postnatal day 3 in these animals although some Sertoli cells survive into adulthood. There is massive germ cell apoptosis in these animals and by 6 months of age the architecture of the testis has degenerated with only rare tubules remaining among an apparent abundance of interstitial tissue (Papaioannou et al ., 2009). This model is interesting in so far as the role of Dicer in the Sertoli cells is concerned but it does not meet all the criteria for a good experimental model of Sertoli cell ablation –that is it cannot be precisely controlled and it does not act quickly.…”