Dicer1 ablation in the mouse epididymis causes dedifferentiation of the epithelium and imbalance in sex steroid signaling.
BACKGROUND
The postnatal development of the epididymis is a complex process that results in a highly differentiated epithelium, divided into several segments. Recent studies indicate a role for RNA interference (RNAi) in the development of the epididymis, however, the actual requirement for RNAi has remained elusive. Here, we present the first evidence of a direct need for RNAi in the differentiation of the epididymal epithelium.


RESULTS
By utilizing the Cre-LoxP system we have generated a conditional knock-out of Dicer1 in the two most proximal segments of the mouse epididymis. Recombination of Dicer1, catalyzed by Defb41(iCre/wt), took place before puberty, starting from 12 days postpartum. Shortly thereafter, downregulation of the expression of two genes specific for the most proximal epididymis (lipocalin 8 and cystatin 8) was observed. Following this, segment development continued until week 5 at which age the epithelium started to regress back to an undifferentiated state. The dedifferentiated epithelium also showed an increase in estrogen receptor 1 expression while the expression of androgen receptor and its target genes; glutathione peroxidase 5, lipocalin 5 and cysteine-rich secretory protein 1 was downregulated, indicating imbalanced sex steroid signaling.


CONCLUSIONS
At the time of the final epididymal development, Dicer1 acts as a regulator of signaling pathways essential for maintaining epithelial cell differentiation.
Department of Physiology, Institute of Biomedicine, University of Turku, Turku, Finland.
Ida
I
Björkgren
Lauri
L
Saastamoinen
Anton
A
Krutskikh
Ilpo
I
Huhtaniemi
Matti
M
Poutanen
Petra
P
Sipilä
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D054337:Cell Dedifferentiation / Q000502:physiology*; D015891:Cystatins / Q000378:metabolism; D053487:DEAD-box RNA Helicases / Q000172:deficiency* / Q000235:genetics; D004822:Epididymis / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D004847:Epithelial Cells / Q000502:physiology*; D047628:Estrogen Receptor alpha / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D055786:Gene Knockout Techniques; D012739:Gonadal Steroid Hormones / Q000378:metabolism*; D006652:Histological Techniques; D007150:Immunohistochemistry; D054834:Lipocalins / Q000378:metabolism; D008297:Male; D051379:Mice; D034622:RNA Interference; D011944:Receptors, Androgen / Q000378:metabolism; D043244:Ribonuclease III / Q000172:deficiency* / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics*; D023083:beta-Defensins / Q000378:metabolism
D015891:Cystatins; D047628:Estrogen Receptor alpha; D012739:Gonadal Steroid Hormones; C423382:Lcn8 protein, mouse; D054834:Lipocalins; D011944:Receptors, Androgen; D023083:beta-Defensins; C078310:Cst8 protein, mouse; C509781:Dicer1 protein, mouse; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases