Chlorogenic Acid Ameliorates Chronic Unpredictable Stress-Induced Diminished Ovarian Reserve Through Ovarian Renin-Angiotensin System

Chronic stress could impair ovarian reserve through hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis, leading to reduced oocyte quality and endocrine dysfunction. The ovarian renin-angiotensin system (OVRAS) modulates follicular development, and excessive activation of the ACE-AngII-AT1R axis increases oxidative stress, disrupting ovarian function. This study investigates OVRAS's role in chronic unpredictable stress (CUS)-induced diminished ovarian reserve (DOR) and explores the protective effects of chlorogenic acid (CGA). Female mice were subjected to CUS (10 intervention methods were randomly applied to mice according to low, medium, and high frequency) and CGA treatment. Hormone levels, estrous cycles, ovarian morphology, oxidative stress, and apoptosis were evaluated. Results demonstrated that CUS overactivated the ACE-AngII-AT1R axis, increasing oxidative stress and apoptosis in granulosa cells (GCs). CGA improved ovarian function, reduced oxidative stress, and downregulated ACE-AngII-AT1R axis activity. CGA may alleviate stress-induced DOR by mitigating oxidative stress and apoptosis via modulation of the ACE-AngII-AT1R axis.