Maternal obesity disrupts epigenetic reprogramming via peroxisomal-dependent phospholipid-methyl uncoupling during zygotic genome activation - PubMed
3 hours ago
- #epigenetics
- #maternal obesity
- #embryonic development
- Maternal obesity disrupts epigenetic reprogramming during zygotic genome activation (ZGA).
- Obesity causes lipid dysregulation, impairing very-long-chain fatty acids (VLCFAs) storage in oocytes and peroxisomal function in embryos.
- Peroxisomal β-oxidation normally converts VLCFAs into medium- and long-chain fatty acids, driving phospholipid methylation and H3K4me3 erasure for ZGA.
- In obese mice, VLCFA deficiency and PEX13 dysfunction lead to metabolic-epigenetic uncoupling, suppressing ZGA and blastocyst development.
- Supplementing long-chain fatty acids or overexpressing PEMT can restore phospholipid-methyl coupling, rescuing epigenetic reprogramming and embryonic development.
- The study identifies peroxisomal β-oxidation as a critical metabolic-epigenetic nexus for maternal-to-zygotic transition (MZT).
- Findings offer potential therapeutic strategies to improve fertility in metabolic disorders.