miR-6615-3p-androgen receptor axis modulates granulosa cell fate via the MDM2-p53-BCL2 pathway in hen Prehierarchical follicles.

MicroRNAs (miRNAs) play critical roles in regulating follicular development and atresia by modulating autophagy, apoptosis, and steroidogenesis in granulosa cells (GCs). However, the role of specific miRNAs in these processes remains poorly understood. In this study, we focused on miR-6615-3p to explore its function and molecular mechanism in chicken Prehierarchical follicular granulosa cells (PFGCs). The expression of miR-6615-3p in chicken PFGCs was confirmed by qRT-PCR. Dual-luciferase reporter assays identified the androgen receptor (AR) gene as a direct target of miR-6615-3p. Functional analyses revealed that miR-6615-3p suppressed AR expression, promoted apoptosis, and inhibited both autophagy and steroidogenesis in PFGCs. Together, these results suggest that miR-6615-3p downregulates AR and is associated with reduced MDM2 expression, enhanced p53 activation, and decreased BCL2 expression. This indicates that it may regulate cell fate and steroid hormone synthesis, at least in part, through the MDM2-p53-BCL2 signaling pathway. This study provides new insights into the molecular mechanisms underlying chicken follicular development and highlights miR-6615-3p as a potential molecular marker for improving reproductive performance in poultry.