Single-cell metabolomics reveals that bisphosphoglycerate mutase influences oocyte maturation through glucose...

The spatiotemporal turnover of metabolites is essential for oocyte maturation, embryonic development, and cell lineage differentiation. Here, we analyzed the metabolic profiles of individual living mouse oocytes and studied how bisphosphoglycerate mutase (BPGM), an important maternal factor, influences metabolite regulation during oocyte maturation. We found that BPGM is expressed in mouse follicles, oocytes, and embryos, as well as in human embryos. Notably, deletion of Bpgm significantly reduced the rate of oocyte maturation and reduced mouse fertility, which was observed as reduced pups per litter. Also, the expression levels for meiosis-related genes and genes related to glucose metabolic pathways (glycolysis, tricarboxylic acid cycle, and pentose phosphate pathway) were altered in BPGM-deficient mouse oocytes. We used a highly sensitive, live-cell sampling approach to carry out metabolite assays using induced nanoelectrospray-ionization mass spectrometry technology on 1 picolitre of aspirated cytoplasm from oocytes. BPGM gene disruption impaired glucose metabolism pathways, tyrosine metabolism, and amino acid biosynthesis. Together, our findings indicate that Bpgm participates in oocyte and embryo development, and we demonstrate the feasibility of studying metabolite composition and other phenotypic features of single oocytes.