A regulatory network controlling ovarian granulosa cell death

Area of Science:

• Reproductive biology
• Molecular endocrinology
• Cellular signaling

Background:

• Follicular atresia, driven by granulosa cell (GC) apoptosis, significantly impairs female fertility and accelerates reproductive aging.
• GC apoptosis is a multifaceted process influenced by various regulatory factors, axes, and signaling pathways.

Purpose of the Study:

• To identify and characterize a novel regulatory network governing GC apoptosis and follicular atresia.
• To elucidate the roles of miR-187, NORHA, and NORFA in regulating the transforming growth factor-β (TGF-β) signaling pathway within sow GCs.

Main Methods:

• Investigated the regulatory interactions between miR-187, TGFBR2 mRNA, and the lncRNAs NORHA and NORFA in sow GCs.
• Analyzed the impact of these molecules on TGF-β signaling pathway activation and GC apoptosis.

Main Results:

• miR-187 directly binds to the 5'-UTR of TGFBR2 mRNA, stabilizing it and activating the TGF-β pathway to suppress GC apoptosis.
• The pro-apoptotic lncRNA NORHA sponges miR-187, thereby inhibiting TGF-β signaling.
• The lncRNA NORFA enhances miR-187 and TGFBR2 expression by inhibiting NORHA and activating NFIX, consequently suppressing GC apoptosis.

Conclusions:

• A novel, concise regulatory network involving miR-187, NORHA, and NORFA controls GC apoptosis and follicular atresia.
• This network, centered around TGF-β pathway modulation, offers new mechanistic insights into GC apoptosis, follicular atresia, and female fertility regulation.