miR-484 mediates oxidative stress-induced ovarian dysfunction and promotes granulosa cell apoptosis via SESN2...

Area of Science:

• Reproductive Biology
• Molecular Endocrinology
• Cellular Stress Response

Background:

• Ovarian dysfunction, a key factor in female infertility, is influenced by genetic, autoimmune, and environmental factors.
• Granulosa cells (GCs) are crucial for ovarian function, and their dysfunction, often linked to oxidative stress (OS) and reactive oxygen species (ROS), contributes to infertility.
• MicroRNA-484 (miR-484) is implicated in ovarian OS and GC function.

Purpose of the Study:

• To investigate the role of miR-484 in ovarian oxidative stress and granulosa cell dysfunction.
• To elucidate the function of the LINC00958/miR-484/Sestrin2 (SESN2) signaling axis in regulating mitochondrial function and apoptosis in GCs under oxidative stress.

Main Methods:

• Utilized 3-NP-induced oxidative stress models in ovaries and GCs.
• Employed bioinformatic analyses, luciferase assays, and pull-down assays to identify interactions within the LINC00958/miR-484/SESN2 axis.
• Assessed the impact of miR-484 manipulation on GC dysfunction, ovarian oxidative stress, mitochondrial function, and apoptosis.

Main Results:

• miR-484 was highly expressed in ovarian oxidative stress models and aggravated GC dysfunction and ovarian injury.
• LINC00958 functioned as a competing endogenous RNA (ceRNA) for miR-484, forming a signaling axis with SESN2.
• This axis regulated mitochondrial function and mitochondria-related apoptosis in GCs, with miR-484 inhibition alleviating dysfunction.

Conclusions:

• miR-484 plays a significant role in ovarian and granulosa cell oxidative stress.
• The LINC00958/miR-484/SESN2 axis is a critical regulator of mitochondrial function and apoptosis in GCs under oxidative stress conditions.
• Inhibition of miR-484 shows potential for alleviating GC dysfunction in ovarian oxidative stress.