Chronic unpredictable stress induces anxiety-like behavior and oxidative stress, leading to diminished ovarian reserve

Abstract

Chronic stress can adversely affect the female reproductive endocrine system, potentially leading to disorders and impairments in ovarian function. However, current research lacks comprehensive understanding regarding the biochemical characteristics and underlying mechanisms of ovarian damage induced by chronic stress. We established a stable chronic unpredictable stress (CUS)-induced diminished ovarian reserve (DOR) animal model. Our findings demonstrated that prolonged CUS treatment over eight weeks resulted in increased atresia follicles in female mice. This atresia was accompanied by decreased AMH and increased FSH levels. Furthermore, we observed elevated levels of corticosterone both in the peripheral blood and within the ovary. Additionally, we detected abnormalities in ATP metabolism within the ovarian tissue. CUS exposure led to oxidative stress in the ovaries, fostering a microenvironment characterized by oxidative damage to mouse ovarian granulosa cells (mGCs) and heightened levels of reactive oxygen species. Furthermore, CUS prompted mGCs to undergo apoptosis via the mitochondrial pathway. These findings indicate a direct association between the fundamental physiological alterations leading to DOR and the oxidative phosphorylation processes within mGCs. The diminished ATP production by mGCs, triggered by CUS, emerges as a pivotal indicator of CUS-induced DOR. Our study establishes an animal model to investigate the impact of chronic stress on ovarian reserve function and sheds light on potential mechanisms underlying this phenomenon.