DICER1 regulates antibacterial function of epididymis by modulating transcription of β-defensins

Area of Science:

• Reproductive biology
• Molecular genetics
• Biochemistry

Background:

• DICER1 enzyme and microRNAs are implicated in male fertility.
• The precise mechanisms of DICER1 in the epididymis require further investigation.

Purpose of the Study:

• To investigate the role of DICER1 in the epididymis and its impact on male fertility.
• To elucidate the mechanism by which DICER1 affects epididymal function.

Main Methods:

• Generation of a mouse model with targeted disruption of the Dicer1 gene in epididymal principal cells.
• Analysis of β-defensin gene expression and DICER1 enrichment at gene promoters.
• Assessment of epididymis antibacterial activity in vitro and in vivo.
• Evaluation of reproductive performance in Dicer1-deficient male mice.

Main Results:

• DICER1, not microRNAs, downregulated a set of β-defensin genes.
• DICER1 was enriched in the promoter of β-defensin genes, controlling their transcription.
• Dicer1 deletion significantly reduced epididymis antibacterial ability.
• Middle-aged Dicer1-/- males exhibited a higher incidence of reproductive defects.

Conclusions:

• DICER1 plays a crucial role in the transcription of β-defensin genes independently of microRNAs.
• The antibacterial properties of the epididymis are influenced by DICER1-mediated β-defensin gene transcription.
• Dysregulation of DICER1 impacts male fertility through altered epididymal function.