Nicotinamide Mononucleotide Supplementation Reverses the Declining Quality of Maternally Aged Oocytes.

Advanced maternal age is highly associated with a decline in oocyte quality, but effective approaches to improve it have still not been fully determined. Here, we report that in vivo supplementation of nicotinamide mononucleotide (NMN) efficaciously improves the quality of oocytes from naturally aged mice by recovering nicotinamide adenine dinucleotide (NAD+) levels. NMN supplementation not only increases ovulation of aged oocytes but also enhances their meiotic competency and fertilization ability by maintaining the normal spindle/chromosome structure and the dynamics of the cortical granule component ovastacin. Moreover, single-cell transcriptome analysis shows that the beneficial effect of NMN on aged oocytes is mediated by restoration of mitochondrial function, eliminating the accumulated ROS to suppress apoptosis. Collectively, our data reveal that NMN supplementation is a feasible approach to protect oocytes from advanced maternal age-related deterioration, contributing to the improvement of reproductive outcome of aged women and assisted reproductive technology.

Coenzyme Q10 ameliorates the quality of postovulatory aged oocytes by suppressing DNA damage and apoptosis.

Postovulatory aging is known to compromise the oocyte quality as well as subsequent embryo development in many different animal models, and becomes one of the most intractable issues that limit the outcome of human assisted reproductive technology (ART). However, the strategies to prevent the deterioration of aged oocytes and relevant mechanisms are still underexplored. Here, we find that supplementation of CoQ10, a natural antioxidant present in human follicular fluids, is able to restore the postovulatory aging-induced fragmentation of oocytes and decline of fertilization. Importantly, we show that CoQ10 supplementation recovers postovulatory aging-caused meiotic defects such as disruption of spindle assembly, misalignment of chromosome, disappearance of actin cap, and abnormal distribution patterns of mitochondria and cortical granules. In addition, CoQ10 protects aged oocytes from premature exocytosis of ovastacin, cleavage of sperm binding site ZP2, and loss of localization of Juno, to maintain the fertilization potential. Notably, CoQ10 suppresses the aging-induced oxidative stress by reducing the levels of superoxide and DNA damage, ultimately inhibiting the apoptosis. Taken together, our findings demonstrate that CoQ10 supplementation is a feasible and effective way to prevent postovulatory aging and preserve the oocyte quality, potentially contributing to improve the successful rate of IVF (in vitro fertilization) and ICSI (intracytoplasmic sperm injection) during human ART.

The protective role of melatonin in porcine oocyte meiotic failure caused by the exposure to benzo(a)pyrene.

STUDY QUESTION: Does melatonin restore the benzo(a)pyrene (BaP)-induced meiotic failure in porcine oocytes? SUMMARY ANSWER: Melatonin effectively inhibits the increased reactive oxygen species (ROS) level and apoptotic rate in BaP-exposed porcine oocytes to recover the meiotic failure. WHAT IS KNOWN ALREADY: BaP, a widespread environmental carcinogen found in particulate matter, 2.5 µm or less (PM2.5), has been shown to have toxicity at the level of the reproductive systems. BaP exposure disrupts the steroid balance, alters the expression of ovarian estrogen receptor and causes premature ovarian failure through the rapid depletion of the primordial follicle pool. In addition, acute exposure to BaP has transient adverse effects on the follicle growth, ovulation and formation of corpora lutea, which results in transient infertility. STUDY DESIGN, SIZE, DURATION: Porcine oocytes were randomly assigned to control, BaP-exposed and melatonin-supplemented groups. BaP was dissolved in dimethylsulphoxide and diluted to a final concentration of 50, 100 or 250 µM with maturation medium, respectively. Melatonin was dissolved in the absolute ethanol and diluted with maturation medium to a final concentration of 1 nM, 100 nM, 10 µM and 1 mM, respectively. The in vitro cultured oocytes from each group after treatment were applied to the subsequent analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Acquisition of oocyte meiotic competence was assessed using immunostaining, fluorescent intensity quantification and/or immunoblotting to analyse the cytoskeleton assembly, mitochondrial integrity, cortical granule dynamics, ovastacin distribution, ROS level and apoptotic rate. Fertilization ability of oocytes was examined by sperm binding assay and IVF. MAIN RESULTS AND THE ROLE OF CHANCE: BaP exposure resulted in the oocyte meiotic failure (P = 0.001) via impairing the meiotic apparatus, showing a prominently defective spindle assembly (P = 0.003), actin dynamics (P < 0.001) and mitochondrion integrity (P < 0.001). In addition, BaP exposure caused the abnormal distribution of cortical granules (P < 0.001) and ovastacin (P = 0.003), which were consistent with the observation that fewer sperm bound to the zona pellucida surrounding the unfertilized BaP-exposed eggs (P < 0.001), contributing to the fertilization failure (P < 0.001). Conversely, melatonin supplementation recovered, at least partially, all the meiotic defects caused by BaP exposure through inhibiting the rise in ROS level (P = 0.015) and apoptotic rate (P = 0.001). LIMITATIONS, REASONS FOR CAUTION: We investigated the negative impact of BaP on the oocyte meiotic maturation in vitro, but not in vivo. WIDER IMPLICATIONS OF THE FINDINGS: Our findings not only deeply clarify the potential mechanisms of BaP-induced oocyte meiotic failure, but also extend the understanding about how environmental pollutants influence the reproductive systems in humans. STUDY FUNDING/COMPETING INTERESTS: This study was supported by the National Natural Science Foundation of China (31571545) and the Natural Science Foundation of Jiangsu Province (BK20150677). The authors have no conflict of interest to disclose.