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

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

  • Mol Hum Reprod. 2025 Apr 3;31(2):gaaf009. doi: 10.1093/molehr/gaaf009.
Jing Wang 1 2 3,  Qiang Liu 1 2 3,  Zhiqiang Yan 1 2 3,  Qianying Guo 1 2 3,  Yixuan Wu 1 2 3,  Ling Ding 1 2 3,  Tianyi Liao 1 2 3,  Jiahui Fan 1 2,  Jie Qiao 1 2 3 4 5 6 7,  Liying Yan 1 2 3
Affiliations

Affiliations

  • 1 Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Peking University Third Hospital, Beijing, China.
  • 2 National Clinical Research Center for Obstetrics and Gynecology (Peking University Third Hospital), Beijing, China.
  • 3 State Key Laboratory of Female Fertility Promotion, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.
  • 4 Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing, China.
  • 5 Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology (Peking University Third Hospital), Beijing, China.
  • 6 Beijing Advanced Innovation Center for Genomics, Peking University, Beijing, China.
  • 7 Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.
PMID: 40323314 DOI: 10.1093/molehr/gaaf009
Abstract

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.

Keywords

BPGM; embryo; oocyte; single-cell RNA-seq; single-cell metabolomics.

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