Work

Quercetin ameliorates oxidative stress in BMP15-deficient oocytes by regulating the ERK1/2-GSK3β-CypD pathway

Year: 2025

Type: article

Abstract: Bone morphogenetic protein 15 (BMP15) is an oocyte-secreted growth factor, which interacts with ovarian follicular somatic cells and in turn promotes oocyte maturation. Disrupting BMP15 by CRISPR-ctRNP has been found to severely impair in vitro maturation (IVM) of porcine oocytes, accompanied with mitochondrial dysfunction and increased accumulation of reactive oxygen species (ROS). To investigate whether the plant-derived antioxidant quercetin (QUE) is able to rescue the IVM of BMP15 -deficient oocytes, porcine oocytes microinjected with CRISPR-ctRNP targeting BMP15 were treated with 10 μM QUE, and we found that QUE can effectively rescue the impaired IVM of BMP15 -deficient oocytes by restoring the impaired mitochondrial functions and reducing ROS through activating extracellular signal-regulated kinase 1/2 (ERK1/2) pathway. Activated ERK1/2 in turn inactivated glycogen synthase kinase-3β (GSK3β), which subsequent reduced Cyclophilin D (CypD) levels, and probably modulated the status the permeability transition pore (PTP) of mitochondria, contributing to the reduced oxidative stress and apoptosis in porcine oocytes, and thus the improved oocyte quality and IVM. Our study further revealed the molecular mechanisms of QUE on alleviating oxidative stress of BMP15 -deficient oocytes, suggesting that QUE may be a promising candidate for improving quality of oocytes with BMP15 mutations. • Quercetin (QUE) effectively rescues impaired in vitro maturation of BMP15 -deficient porcine oocytes through alleviating oxidative stress and apoptosis • Specific interactions between QUE and ERK1/2 proteins rescued mitochondrial functions and reduced reactive oxygen species (ROS) accumulation in BMP15 -deficient porcine oocytes • The reduced mitochondrial functions were attributed to the restored activation of ERK1/2 signaling by QUE, which inactivated GSK3β and inhibited CypD expression, modulating the status of permeability transition pore (PTP).

Source: Redox Biology

DOI: 10.1016/j.redox.2025.103886