Increased mtDNA mutation frequency in oocytes causes epigenetic alterations and embryonic defects.

ABSTRACT: Mitochondria are essential for female reproductive processes, yet the function of mitochondrial DNA (mtDNA) mutation in oocytes remains elusive. By employing an mtDNA mutator (Polg^m) mouse model, we found the fetal growth retardation and placental dysfunction in post-implantation embryos derived from Polg^m oocytes. Remarkably, Polg^m oocytes displayed the global loss of DNA methylation; following fertilization, zygotic genome experienced insufficient demethylation, along with dysregulation of gene expression. Spindle-chromosome exchange experiment revealed that cytoplasmic factors in Polg^m oocytes are responsible for such a deficient epigenetic remodeling. Moreover, metabolomic profiling identified a significant reduction in the α-ketoglutarate (α

SUBMITTER: Han L 

PROVIDER: S-EPMC9616472 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature