Roles of endoplasmic reticulum stress in the pathophysiology of polycystic ovary syndrome

Abstract

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among reproductive-age women, affecting up to 15% of women in this group, and the most common cause of anovulatory infertility. Although its etiology remains unclear, recent research has revealed the critical role of endoplasmic reticulum (ER) stress in the pathophysiology of PCOS. ER stress is defined as a condition in which unfolded or misfolded proteins accumulate in the ER because of an imbalance in the demand for protein folding and the protein-folding capacity of the ER. ER stress results in the activation of several signal transduction cascades, collectively termed the unfolded protein response (UPR), which regulates various cellular activities. In principle, the UPR restores homeostasis and keeps the cell alive. However, if the ER stress cannot be resolved, it induces programmed cell death. ER stress has recently been recognized to play diverse roles in both physiological and pathological conditions of the ovary. In this review, we summarize current knowledge of the roles of ER stress in the pathogenesis of PCOS. ER stress pathways are activated in the ovaries of both a mouse model of PCOS and in humans, and local hyperandrogenism in the follicular microenvironment associated with PCOS is responsible for activating these. The activation of ER stress contributes to the pathophysiology of PCOS through multiple effects in granulosa cells. Finally, we discuss the potential for ER stress to serve as a novel therapeutic target for PCOS.

Pathophysiological Effects of Contemporary Lifestyle on Evolutionary-Conserved Survival Mechanisms that Disturb the Hallmarks of Health in Polycystic Ovary Syndrome

“…Oxidative stress has been reported to enhance ovarian steroidogenic enzymes and increase androgen levels in women with PCOS (162). Endoplasmic reticular stress pathways are activated in the ovaries in mouse models and in humans, and may contribute to the pathophysiology of PCOS through multiple effects in granulosa cells (163,164). As discussed previously, AGE and RAGE have been found to cause altered steroidogenesis in granulosa cells in PCOS (99).…”

Cannabinoid Combination TargetsNOTCH1-Mutated T-ALL Through the Integrated Stress Response Pathway

“…The potential antitumor effects of cannabinoids through the Notch1 signaling pathway were previously demonstrated in glioma, where THC induced the expression of p8 protein, upstream to ATF3/4 ( 57 ). The activation of Notch signaling by ER stress was demonstrated in additional systems, including Alzheimer’s disease ( 58 ), polycystic ovary syndrome ( 59 ) and other types of cancer ( 60 , 61 ). A previous work that focused on chronic lymphocytic leukemia suggested a role for ER stress in Notch1 cleavage and leukemia cell death through the inhibition of proteasome activity ( 62 ).…”

Research progress on the beneficial effects of exercise on endocrine system-related diseases in women by regulating ER stress pathways

“…Research has found that the relative expression of BIP mRNA and protein was signi cantly higher in the PCOS observation group than in the control group; similarly, the relative expression of CHOP mRNA and protein tended to be higher in the PCOS observation group than in the control group, although there was no signi cant difference [79]. The result several genes involved in UPR er and UPR mt were overexpressed in the GCs of PCOS-IR.…”