Nicotinamide mononucleotide supplementation reverses the declining quality of maternally aged oocytes

Advanced maternal age, defined as 35 years or older, is associated with a decline in both ovarian reserve and oocyte quality, which leads to the female infertility, pregnancy loss, fetal anomalies, stillbirth, and obstetric complications. At present, the effective approaches to counteract the maternal age-related decay of oocyte quality are still not fully determined. Here, we report that in vivo supplementation of nicotinamide mononucleotide (NMN) efficaciously ameliorates the quality of oocytes from naturally aged mice by recovering nicotinamide adenine dinucleotide (NAD + ) levels in oocytes. NMN supplementation increases the number of antral follicles, ovulated oocytes and matured oocytes from aged mice. Specifically, NMN supplementation maintains the normal spindle/chromosome structure and dynamics of cortical granule component ovastacin to ensure the meiotic competency and fertilization ability of aged oocytes. Moreover, single cell transcriptome analysis shows that the beneficial effect of NMN on the aged oocytes is mediated by the restoration of the mitochondrial function, thereby reducing the accumulated ROS to suppress the occurrence of apoptosis. To sum up, our data reveal that supplementation of NMN is a feasible approach to prevent oocyte quality from advanced maternal age-related deterioration, contributing to improve the reproductive outcome of aged women and the assisted reproductive technology. Transcriptomic analysis of matured oocytes was carried out using a protocol for single cell RNA-Seq. The constructed library was sequenced with Illumina platform.