Page 92 - PRECONGRESS COURSE 03

Ovarian reserve and DNA damage
Follicle number decreases over time, until menopause
Common genetic variants of the DNA damage response determines the AGE OF NATURAL ONSET of menopause
Premature depletion: premature ovarian insufficiency (POI) Pathogenic variants for BRCA1 and STAG3 predispose to POI
(Titus et al., 2013, Caburet et al. 2014)
(Day et al., 2015)
Conclusions
• DNA damage is both good and bad.
• DNA damage and repair regulates the age of natural onset of menopause
• DNA damage response genes are also implicated in premature ovarian insufficiency
• Chromosome errors in segregation lead to aneuploidy (extra or missing chromosomes).
• DNA damage is detrimental in embryos (no programmed induction of damage).
• DNA damage and chromosome instability in embryos restrict their developmental potential.
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