Dicer is required for Sertoli cell function and survival.
Dicer is a key enzyme that processes microRNA precursors into their mature form, enabling them to regulate gene expression. Dicer null mutants die before gastrulation. To study Dicer function in testis development, we crossed mice carrying a conditional Dicer allele with an AMH-Cre transgenic line, thereby inactivating Dicer in Sertoli cells around embryonic day 14.0 (E14.0). Dicer null Sertoli cells show normal embryonic development, and at postnatal day 0 (P0), testis tubules are normal in number and histologically undistinguishable from controls. Subsequently, Dicer-mutant testes show a progressively aberrant development, so that at P6, they contain a reduced number of disorganized testis tubules leading to primary sterility. Apoptosis and prophase I assays reveal a massive wave of apoptosis starting at P3, causing progressive loss of Sertoli cells, but also of germ cells, resulting in drastically reduced testis size. Expression of genes that play crucial roles in testis development, structural integrity and spermatogenesis is downregulated at P0, before morphological changes become apparent, indicating that Dicer-mutant testes are already transcriptionally compromised at this stage. Taken together, the results of this study show that Dicer is required for Sertoli cell function and survival and for spermatogenesis in mice.
Kim
Gwang-Jin
GJ
Institute of Human Genetics, University of Freiburg, Germany.
Georg
Ina
I
Scherthan
Harry
H
Merkenschlager
Matthias
M
Guillou
Florian
F
Scherer
Gerd
G
Barrionuevo
Francisco
F
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D004722:Endoribonucleases / Q000235:genetics / Q000378:metabolism*; D005260:Female; D007150:Immunohistochemistry; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D043244:Ribonuclease III; D012708:Sertoli Cells / Q000166:cytology / Q000378:metabolism*; D013091:Spermatogenesis / Q000235:genetics / Q000502:physiology*; D013737:Testis / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D013997:Time Factors
D008164:Luminescent Proteins; D004722:Endoribonucleases; C509781:Dicer1 protein, mouse; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases