Nampt affects mitochondrial function in aged oocytes by mediating the downstream effector FoxO3a

Abstract

Maternal aging can impair the quality and decrease the developmental competence of ovulated oocytes. In this study, compromised germinal vesicle breakdown (GVBD) was found in aged mice oocytes. Furthermore, we observed increased reactive oxygen species (ROS) and mitochondrial Ca2+ levels, along with reduced mitochondrial temperature in aged oocytes. Maternal aging also changed the crotonylation level in oocytes. Forkhead box O3 (FoxO3a), a member of the forkhead protein family involved in the regulation of cell survival and life span reached a peak level in the metaphase II stage. Compared with a younger group, FoxO3a expression increased in aged oocytes. Intracellular localization of FoxO3a changed from the cytoplasm to chromatin in response to aging. The expression of the upstream regulator nicotinamide‐phosphoribosyltransferase (Nampt) peaked in the GVBD stage. Moreover, Nampt expression was increased in aged oocytes, and more intense staining of Nampt was found in aged mice ovary. To further study the role of Nampt in mitochondrial function, specific agonist P7C3 and inhibitor FK866 were applied to aged oocytes, and FK866 significantly decreased adenosine triphosphate and mitochondrial membrane potential. In conclusion, mitochondrial dysfunction in aged oocytes was associated with elevated FoxO3a, and suppression of Nampt could further impair mitochondrial function.

Procyanidin B2 Protects Aged Oocytes Against Meiotic Defects Through Cortical Tension Modulation

“…In agreement with our previous findings, the GVBD rate was significantly decreased in the aged oocytes, while the PBE rate was similar (16). As we pointed out in our previous report, aged oocytes underwent both GVBD and PBE more slowly than young oocytes, this indicated that the meiotic process in the aged oocytes was disrupted to a certain extent (16). In the present study, we found PCB2 supplementation can significantly improve the GVBD rate in aged oocytes (Figure 1).…”

“…We previously found that 5 µg/mLPCB2 supplementation during in vitro maturation progress could attenuate meiosis defects, improve the subsequent developmental potential after parthenogenetic activation of diabetic mouse oocytes (12). In agreement with our previous findings, the GVBD rate was significantly decreased in the aged oocytes, while the PBE rate was similar (16). As we pointed out in our previous report, aged oocytes underwent both GVBD and PBE more slowly than young oocytes, this indicated that the meiotic process in the aged oocytes was disrupted to a certain extent (16).…”

“…Our previous study indicated that reproductive aging can impair mitochondrial function and further induce increased ROS levels in oocytes (16). Therefore, we further investigated whether PCB2 treatment could alleviate the oxidative stress in aged oocytes.…”

Resveratrol and SIRT1: Antiaging Cornerstones for Oocytes?

“…In older oocytes, in addition to increased concentrations of reactive oxygen species, mitochondrial damage, increased meiotic errors, autophagy, and premature apoptosis are noted [ 11 , 56 ]. In addition to reduced oocyte quality, excessive aging can lead to slower passage through the developmental phases, as indicated in pigs [ 57 ]. SIRT1 is a protein whose activity is strongly associated with states of elevated concentrations of reactive oxygen species and has been proven to mitigate oocyte aging [ 58 ], and loss of SIRT1 causes increased oocyte aging [ 59 ].…”

Mitochondrial Calcium Disorder Affects Early Embryonic Development in Mice through Regulating the ERK/MAPK Pathway

“…Obese, diabetic, and aging women having lower rate of oocyte activation, altered preimplantation embryo development, and even lower pregnancy rates have been highlighted [26][27][28][29], and these disorders have been related to the mitochondrial dysfunction in oocytes [5], because the ATP production and oxidative phosphorylation are essential for reproductive cellular processes including meiotic maturation and postimplantation development [30]. Our previous stud- We further found that the spindle/chromosome structure was damaged in drug-treated MII oocytes (Figures 2(a)-2(d)), indicating that oocytes are in poor quality, also supporting our previous studies that the depletion of MCU markedly disrupts spindle formation during oocyte meiosis [10].…”