Anti-Aging Effect of Urolithin A on Bovine Oocytes In Vitro

SIMPLE SUMMARY: Post-ovulatory and maternal oocyte aging impair female reproductive capacity through several mechanisms that are not fully understood. Urolithin A (UA) is a natural compound previously identified to exert an anti-aging effects in several cells, which has never been used in bovine germinal cells. Our goal was to study UA effect on the developmental potential of the female gamete and the surround cumulus cells obtained from young and adult cows. A model for in vitro aging of female gametes was implemented to study different problems associated with reproductive aging and fertility impairment. Results confirmed that aging exerts a harmful effect on oocyte quality measured by using different parameters and gene expression levels of cumulus cells. Moreover, UA supplementation was an effective way to prevent oocyte aging, improving the subsequent bovine embryonic development. ABSTRACT: Oxidative stress and mitochondrial dysfunction have been associated with the age-related decline of oocyte quality and strategies for their prevention are currently quested. Urolithin A (UA) is a natural metabolite with pro-apoptotic and antioxidant effects, capable of preventing the accumulation of dysfunctional mitochondria in different aged cells. UA has never been tested in bovine oocytes. Our aim was to study the effect of UA on the developmental potential of cumulus-oocyte-complexes (COCs) and granulosa cells’ (GCs) expression of important genes related to reproductive competence. Nuclear maturation progression, mitochondrial membrane potential (MMP) and developmental competence of physiologically mature (22 h) and in vitro aged oocytes (30 h of IVM) obtained from prepubertal and adult females, either supplemented with UA or not were assessed. Additionally, the amount of mRNA of several genes (NFE2L2, NQO1, and mt-DN5) and the number of mt-ND5 DNA copies were quantified in cultured GCs from prepubertal and adult females, either supplemented with UA or not. Our study confirmed the harmful effect of oocyte aging on the nuclear maturation progression, MMP, developmental competence and gene expression levels. UA treatment during in vitro maturation enhanced (p < 0.05) the maturation rate and subsequent developmental capacity of aged oocytes. A positive effect (p < 0.05) of UA on physiological maturation, MMP and embryonic development was also identified. UA also interfered on the expression profile of NFE2L2 and NQO1 genes in GCs cultures. Our findings demonstrate that UA supplementation is an effective way to prevent oocyte aging and improves the subsequent bovine embryonic development.