Endometriosis, a painful and often debilitating condition affecting millions of women worldwide, has long been linked to oxidative stress—an imbalance between harmful reactive oxygen species (ROS) and antioxidant defenses. Despite evidence that antioxidants can help manage symptoms (chronic pelvic pain and infertility), the exact mechanisms behind their effects have remained unclear. Now, groundbreaking research sheds new light on how oxidative stress affect endometriosis and points to potential therapeutic strategies.
In a study published in Science Bulletin, researchers discovered that endometrial stromal cells (ESCs) exposed to moderate ROS levels develop increased cell vitality and resistance to senescence, which contribute to endometriosis progression. The team identified checkpoint kinase 1 (CHK1) as a crucial sensor of ROS in ESCs. Exposing to moderate ROS, CHK1 moves from the nucleus to the cytoplasm, where it stabilizes the downstream target, serum/glucocorticoid-regulated kinase 1 (SGK1), by controlling its breakdown.
Remarkably, silencing SGK1 significantly reduced the survival and anti-aging effects of ROS in ESCs. In mouse models, the antioxidant N-acetylcysteine (NAC) successfully restrict lesion growth by reducing ROS and suppressing CHK1/SGK1 activity. Additionally, inhibitors specifically targeting CHK1 or SGK1 also effectively suppress lesion growth.
"These findings provide a missing piece in the puzzle of endometriosis development," said the study's lead researcher. "By understanding how the CHK1/SGK1 axis helps endometrial cells thrive under stress, we can now explore more precise ways to disrupt this process—potentially leading to better treatments."
The study not only deepens our understanding of endometriosis but also highlights promising drug targets that could pave the way for more effective therapies, offering renewed hope for patients struggling with this chronic condition.
Journal
Science Bulletin