Abstract
Maternal fertility declines irreversibly with aging, and advanced maternal age is mostly related to impaired oocyte quality. The flavonol compound quercetin is considered to be an anti-aging agent due to its cytoprotective actions as an antioxidant. However, its role and mechanisms on aged oocytes are unclear. In this study, the quercetin promotes in vitro maturation (IVM) and early embryonic development of oocytes from aged mice. It is extended these findings in human oocytes, showing that quercetin promotes the IVM rate by 19.6% and increases the blastocyst formation rate by 15.5% compared to untreated controls. The overall oocyte quality of aged mice is improved by quercetin treatment, assessed as spindle/chromosome morphology and cortical granule distribution. Mitochondria is the primary endogenous source of age-related oxidative stress, and an RNA-seq analysis of quercetin-treated oocytes reveals molecular insights including scavenged mitochondrial-ROS, reduced apoptosis, and improved autophagy. Further, this study demonstrates that quercetin reduces ROS via SIRT3-mediated acetylation of SOD2’s K68 residue. Thus, beyond demonstrating that quercetin confers beneficial mitochondria-related impacts in aged oocytes, this study illustrates a potential strategy to prevent or delay oocyte aging and to improve success rates of assisted human reproductive technologies (ART).
Highlights
The progressive loss of ovarian follicles accelerates with aging, especially in humans over the age of 381
Consistent with these findings, our results demonstrated that quercetin had the potential to improve in vitro maturation (IVM) and embryonic developmental competency in aged mice (Fig. 1C)
Detecting that quercetin improves the quality of aged oocytes by reducing the levels of known age-related mitochondrial oxidative stress, reducing the extent of apoptosis, and promoting autophagy
Summary
The progressive loss of ovarian follicles accelerates with aging, especially in humans over the age of 381. Maternal age-related decline in fecundity is associated with increased aneuploidy and poor oocyte maturation, which can lead to detrimental clinical outcomes, for example, congenital anomalies and miscarriage[4]. IVM is a highly impactful procedure used to help retrieve immature oocytes. It is widely used in both scientific research with laboratory animals and human ART, and notable because it facilitates the development of totipotent embryos[8,9,10]. In the clinic, IVM can eliminate the risk of ovarian hyperstimulation syndrome, as it involves only minimal or no prior FSH stimulation, Official journal of the Cell Death Differentiation Association
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