DICER Regulates the Formation and Maintenance of Cell-Cell Junctions in the Mouse Seminiferous Epithelium.
The endonuclease DICER that processes micro-RNAs and small interfering RNAs is essential for normal spermatogenesis and male fertility. We previously showed that the deletion of Dicer1 gene in postnatal spermatogonia in mice using Ngn3 promoter-driven Cre expression caused severe defects in the morphogenesis of haploid spermatid to mature spermatozoon, including problems in cell polarization and nuclear elongation. In this study, we further analyzed the same mouse model and revealed that absence of functional DICER in differentiating male germ cells induces disorganization of the cell-cell junctions in the seminiferous epithelium. We detected discontinuous and irregular apical ectoplasmic specializations between elongating spermatids and Sertoli cells. The defective anchoring of spermatids to Sertoli cells caused a premature release of spermatids into the lumen. Our findings may help also explain the abnormal elongation process of remaining spermatids because these junctions and the correct positioning of germ cells in the epithelium are critically important for the progression of spermiogenesis. Interestingly, cell adhesion-related genes were generally upregulated in Dicer1 knockout germ cells. Claudin 5 ( Cldn5 ) was among the most upregulated genes and we show that the polarized localization of CLAUDIN5 in the apical ectoplasmic specializations was lost in Dicer1 knockout spermatids. Our results suggest that DICER-dependent pathways control the formation and organization of cell-cell junctions in the seminiferous epithelium via the regulation of cell adhesion-related genes.
Institute of Biomedicine, Department of Physiology, University of Turku, Turku, Finland.
Hanna Maria
HM
Korhonen
Institute of Biomedicine, Department of Physiology, University of Turku, Turku, Finland.
Ram Prakash
RP
Yadav
Institute of Biomedicine, Department of Physiology, University of Turku, Turku, Finland.
Matteo
M
Da Ros
Inserm U1085-Irset, Université de Rennes 1, Rennes, France.
Frédéric
F
Chalmel
Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland iGE3, Institute of Genetics and Genomics of Geneva, University of Geneva, Geneva, Switzerland.
Céline
C
Zimmermann
Institute of Biomedicine, Department of Physiology, University of Turku, Turku, Finland Department of Pediatrics, University of Turku, Turku, Finland.
Jorma
J
Toppari
Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland iGE3, Institute of Genetics and Genomics of Geneva, University of Geneva, Geneva, Switzerland.
Serge
S
Nef
Institute of Biomedicine, Department of Physiology, University of Turku, Turku, Finland noora.kotaja@utu.fi.
Noora
N
Kotaja
D000818:Animals; D001814:Blood-Testis Barrier / Q000378:metabolism; D002448:Cell Adhesion / Q000235:genetics*; D062507:Claudin-5 / Q000235:genetics / Q000378:metabolism; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D007365:Intercellular Junctions / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D043244:Ribonuclease III / Q000235:genetics / Q000378:metabolism*; D012670:Seminiferous Epithelium / Q000378:metabolism*; D012708:Sertoli Cells / Q000378:metabolism*; D013087:Spermatids / Q000378:metabolism*; D013091:Spermatogenesis / Q000502:physiology; D015854:Up-Regulation
D062507:Claudin-5; C491511:Cldn5 protein, mouse; C509781:Dicer1 protein, mouse; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases
DICER; apical ectoplasmic specialization; blood-testis barrier; cell-cell junction; gene regulation; miRNA; spermatogenesis