GRSF1 deficiency attenuates mitochondrial function in aging granulosa cells

Area of Science:

• Reproductive Biology
• Cellular Aging
• Mitochondrial Biology

Background:

• Ovarian aging is characterized by decreased oocyte quality and increased oxidative stress.
• Granulosa cells (GCs) play a crucial role in oocyte development and are affected by aging.

Purpose of the Study:

• To investigate the role of guanine-rich RNA sequence binding factor 1 (GRSF1) in ovarian granulosa cell aging.
• To understand the molecular mechanisms by which GRSF1 influences mitochondrial function and oxidative stress in aging GCs.

Main Methods:

• Analysis of GRSF1 levels in GCs from IVF patients of varying ages.
• siRNA-mediated knockdown of GRSF1 in GCs to assess its impact on mitochondrial function, reactive oxygen species (ROS), and ATP production.
• RNA immunoprecipitation to identify GRSF1-interacting mRNAs, specifically focusing on antioxidant enzymes like superoxide dismutase 2 (SOD2).

Main Results:

• GRSF1 levels significantly decrease in GCs with increasing patient age.
• Reduced GRSF1 expression exacerbates mitochondrial dysfunction, increases ROS levels, and impairs ATP production in GCs.
• GRSF1 directly interacts with SOD2 mRNA, and its downregulation reverses the protective effects of GRSF1 on mitochondrial function.

Conclusions:

• GRSF1 deficiency contributes to ovarian granulosa cell aging by impairing mitochondrial function and increasing oxidative stress.
• GRSF1-mediated regulation of SOD2 is a key mechanism protecting against age-related mitochondrial decline in GCs.
• Targeting GRSF1 may offer a therapeutic strategy to improve fertility outcomes in women of advanced reproductive age.