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Genetic Variation and Age of Menopause
(He et al., Nature Genetics, 2011, Laven et al., Maturitas 2016)
 Genes affecting ovarian function seem to play a role in DNA maintenance and DNA repair and as such are involved in both somatic cell and germ line ageing.
 Only SYCP2L is required for protein synthesis in the synaptonemal complex which zips together homologue chromosomes during the first meiotic division !!!!
 All the other SNP’s are referring to genes involved in ageing, DNA repair, DNA maintenance and replication. Hence, only ONE gene might be involved in folliculogenesis
 There is considerable overlap between POI specific variants and those determining natural menopause
 DNA repair of DSB might become less effective with increasing age and simultaneous accumulation of DSB might lead to loss
of oocytes and diminished ovarian reserve
 Could it therefore be that ageing of the soma is the primary driver for the loss of ovarian function in women instead of the old dogma which implies that loss of ovarian function initiates ageing of the soma?
 Time for a Paradigm Shift?
ESHRE Pre Congres Course 8:
Genes Involved in Menopause and POI
DNA MAINTENANCE & REPAIR AND OVARIAN FUNCTION
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PRECONGRESS COURSE 08 I BARCELONA, SPAIN – 1 JULY 2018 77