Oxidative Stress And Sirt1-Nrf2 Anti-Ferroptotic Pathways In Granulosa Cells: A Molecular Key To Follicular Atresia And Ovarian Aging
Our ovaries, crucial for fertility, contain tiny structures called follicles, each housing an egg. Supporting these eggs are specialized cells known as granulosa cells. The health and proper functioning of these granulosa cells are absolutely essential for successful reproduction and determine the overall “age” of our ovaries.
However, these vital cells are constantly under threat from something called oxidative stress. Imagine your body as a machine; oxidative stress is like rust forming due to an imbalance between harmful molecules (oxidants) and protective ones (antioxidants). This “rust” can damage granulosa cells, leading to their dysfunction and a process called follicular atresia, where follicles degenerate prematurely.
Recent research highlights another significant threat: ferroptosis. This is a unique form of cell death that relies on iron and involves the breakdown of fats within cells. It has been identified as a key contributor to granulosa cell death in aging ovaries.
Fortunately, our cells have built-in defense mechanisms. A crucial one is the SIRT1-Nrf2 pathway. Think of this pathway as a cellular shield. SIRT1 helps maintain the health and energy production of mitochondria, the powerhouses of our cells, and keeps our metabolism resilient. Simultaneously, Nrf2 activates a team of protective enzymes that neutralize harmful substances and directly prevent ferroptosis.
When this protective SIRT1-Nrf2 pathway is disrupted, granulosa cells become more vulnerable, accelerating ovarian aging and leading to a decline in fertility. Understanding this intricate molecular key opens up new possibilities for developing treatments to preserve fertility and potentially delay ovarian aging.
Source: link to paper