Granulosa Cell MYC Sustains Oocyte Quality Through Glycerophospholipid Metabolism in Mice

A gene called Myc, active in the granulosa cells that surround developing eggs, appears to be essential for female fertility in mice, according to a new study published in Cellular & Molecular Biology Letters. When researchers deleted Myc specifically from mouse granulosa cells, the animals ovulated fewer eggs, and the eggs that were fertilized failed to develop normally into blastocysts, leaving the females infertile. The work, released as a peer-reviewed accepted manuscript with a permanent DOI, points to a metabolic relay between supporting cells and oocytes as a key determinant of egg quality.

The team first mapped where the gene, formally the cellular myelocytomatosis viral oncogene (c-Myc, also known as Myc), is expressed in mouse follicles and found that its mRNA was mainly present in granulosa cells. To test its function, the researchers generated mice with conditional deletion of Myc in these cells. The resulting knockout females showed the reduced ovulation count and the failure of fertilized oocytes to reach the blastocyst stage, establishing that a gene acting in the somatic cells surrounding the egg, rather than in the egg itself, is required for oocytes to complete early embryonic development.

Searching for the mechanism, the investigators found that loss of Myc lowered both the mRNA and protein levels of genes encoding glycerophospholipid metabolic enzymes in the granulosa cells. Metabolite measurements matched this enzymatic downshift: knockout of Myc reduced the pool of glycerophospholipid metabolites in the granulosa cells.

According to the study, the reduction in granulosa-cell glycerophospholipid metabolites was accompanied by decreases in glycerophospholipid metabolites and mitochondrial function in oocytes, which in turn led to more abnormal spindle assembly and aneuploidy, an incorrect number of chromosomes, in the eggs.

The researchers also tested whether the missing metabolites could be replaced. When glycerophospholipid metabolites were added to cultured cumulus–oocyte complexes, the blastocyst rate of knockout mouse oocytes undergoing in vitro fertilization was partially restored.

Because the study was conducted entirely in mice with a targeted gene deletion, its findings cannot be extended directly to human fertility without further research. Even so, the results add to a growing picture in which granulosa cell-produced metabolites sustain the growth and development of mammalian oocytes, and they identify a specific gene-to-metabolite-to-chromosome pathway that could guide future studies of egg quality.

Subject of Research: The role of granulosa cell MYC in maintaining oocyte developmental competence through glycerophospholipid metabolism in mice.

Article Title: Granulosa cell MYC maintains oocyte developmental ability via promoting glycerophospholipid metabolism in mice

Article References: Sun, Y.-L., Zhang, X., Liu, J., Wang, R., Liu, S., Wang, W., Wei, H., Wang, Z., Zhang, W., Han, L., Hao, X., & Zhang, M. (2026). Granulosa cell MYC maintains oocyte developmental ability via promoting glycerophospholipid metabolism in mice. Cellular & Molecular Biology Letters. https://doi.org/10.1186/s11658-026-01013-8

Image Credits: AI Generated

DOI: 10.1186/s11658-026-01013-8

Keywords: MYC, granulosa cells, oocytes, glycerophospholipid metabolism, female infertility, mice, aneuploidy, spindle assembly, mitochondrial function, blastocyst, conditional knockout, fertility