Resveratrol-induced mitochondrial synthesis and autophagy in oocytes derived from early antral follicles of aged cows

Abstract

Mitochondrial numbers increase during oocyte growth. In this study, we collected oocytes and granulosa cell complexes (OGCs) from early antral follicles (EAFs) of aged cows (> 120 months of age) and examined the effects of resveratrol on mitochondrial generation, degradation, and quality in oocytes grown in vitro. We also examined the effects of resveratrol on gene expression of the granulosa cells. Resveratrol (20 µM) enhanced the expression of SIRT1 and induced autophagy in both granulosa cells and oocytes derived from aged cows. Culturing the OGCs with resveratrol increased mitochondrial DNA copy numbers in oocytes grown in vitro. Furthermore, resveratrol increased the ATP content in oocytes and improved the developmental ability of the oocytes to the blastocyst stage. Gene expression profiles in granulosa cells, as evaluated by next-generation sequencing technology, revealed that resveratrol enhanced the expression of EIF2-related genes but downregulated the expression of mammalian target of rapamycin (mTOR)-, inflammation-, and cholesterol homeostasis-related genes in granulosa cells. In conclusion, resveratrol affected both oocytes and granulosa cells derived from aged cows and improved the quality of oocytes grown in vitro through upregulation of mitochondrial biogenesis and degradation in growing oocytes and conditioning of granulosa cells.

Effects of supplementation of medium with different antioxidants during in vitro maturation of bovine oocytes on subsequent embryo production

“…The flavonoids (quercetin and resveratrol), cysteamine (via GSH), vitamin C and carnitine interact with gene expression, altering the expression of certain genes (Bax, Blc‐2, TP53, Oct‐4, Cx‐43, IGF‐1 and Glut‐1), which may cause a likely reduction in cell damage (Choi et al., ; Elamaran et al., ; Kawashima et al., ; Mukherjee et al., ; You, Lee, Hyun, & Lee, ). The antioxidants quercetin, resveratrol, vitamin C and carnitine can also present a protective effect on mitochondrial functions (Carrasco‐Pozo, Mizgier, Speisky, & Gotteland, ; Lee., Li, Chen, & Chang, ; Somfai et al., ; Sugiyama et al., ) to new mitochondrial synthesis in oocytes from antral follicles cultured in vitro with resveratrol. During oocyte growth, there is increase in mitochondrial DNA copy numbers (Cotterill et al., ; Sugiyama et al., ), and the number of mitochondria in mature oocytes is important to determine their developmental capacity (May‐Panloup, Chretien, Malthiery, & Reynier, ).…”

“…The antioxidants quercetin, resveratrol, vitamin C and carnitine can also present a protective effect on mitochondrial functions (Carrasco‐Pozo, Mizgier, Speisky, & Gotteland, ; Lee., Li, Chen, & Chang, ; Somfai et al., ; Sugiyama et al., ) to new mitochondrial synthesis in oocytes from antral follicles cultured in vitro with resveratrol. During oocyte growth, there is increase in mitochondrial DNA copy numbers (Cotterill et al., ; Sugiyama et al., ), and the number of mitochondria in mature oocytes is important to determine their developmental capacity (May‐Panloup, Chretien, Malthiery, & Reynier, ). Oocytes or cells cultured in vitro with antioxidants (quercetin, resveratrol and carnitine) exhibit a significant increase in ATP (adenosine triphosphate) amounts, suggesting that mitochondrial function was improved by the use of these antioxidants (Carrasco‐Pozo et al., ; Dunning et al., ; Sugiyama et al., ).…”

“…During oocyte growth, there is increase in mitochondrial DNA copy numbers (Cotterill et al., ; Sugiyama et al., ), and the number of mitochondria in mature oocytes is important to determine their developmental capacity (May‐Panloup, Chretien, Malthiery, & Reynier, ). Oocytes or cells cultured in vitro with antioxidants (quercetin, resveratrol and carnitine) exhibit a significant increase in ATP (adenosine triphosphate) amounts, suggesting that mitochondrial function was improved by the use of these antioxidants (Carrasco‐Pozo et al., ; Dunning et al., ; Sugiyama et al., ). Supplementation during in vitro maturation with carnitine significantly increases β‐oxidation in mouse oocytes.…”

Preconception resveratrol intake against infertility: Friend or foe?

“…Resveratrol has a therapeutic direct effect on oocytes in in vitro culture. Treating the culture media with resveratrol improves oocyte maturation and the developmental competence of embryos to blastocysts in both animals and humans . Moreover, during IVF treatments, minimization of the time‐dependent deterioration after ovulation (postovulatory oocyte aging) is a key for successful pregnancies.…”

“…The quality and quantity of mitochondria are associated with the balance of mitochondrial biogenesis and autophagy. Resveratrol has effects on mitochondrial biogenesis as well as autophagy in the process of oocyte development, leading to remaining homeostasis in oocytes and granulosa cells through the clearance of damaged mitochondria . Resveratrol also protects postovulatory human granulosa cells from apoptosis by activating the ERK pathway associated with the follicular antiapoptotic effect and by suppressing inflammatory functions of NF‐κB signaling …”