Mitochondrial DNA mutation exacerbates female reproductive aging via impairment of the NADH/NAD⁺ redox.

ABSTRACT: Mammals' aging is correlated with the accumulation of somatic heteroplasmic mitochondrial DNA (mtDNA) mutations. Whether and how aging accumulated mtDNA mutations modulate fertility remains unknown. Here, we analyzed oocyte quality of young (≤30 years old) and elder (≥38 years old) female patients and show the elder group had lower blastocyst formation rate and more mtDNA point mutations in oocytes. To test the causal role of mtDNA point mutations on infertility, we used polymerase gamma (POLG) mutator mice. We show that mtDNA mutation levels inversely correlate with fertility, interestingly mainly affecting not male but female fertility. mtDNA mutations decrease female mice's fertility by reducing ovarian primordial and mature follicles. Mechanistically, accumulation of mtDNA mutations de

SUBMITTER: Yang L 

PROVIDER: S-EPMC7511885 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature