Reduced DNA egg repair may explain age-related fertility fall-off

A slowdown in DNA repair mechanisms, one of
which involves the BRCA genes implicated in cancer, may partly explain why
women's eggs rapidly decline in both quantity and quality in middle age.

Women are born with a million egg
progenitor cells but only around 500 of these will ever be released as eggs, or
oocytes. The remaining cells degrade and die and the reasons behind this have
remained largely obscure.

However speaking to the magazine The Scientist, Dr
Kutluk Oktay, who led the study published in Science Translational Medicine, said:
'I think we have found a general theory of reproductive ageing'.

The study includes work on both mouse and
human oocytes demonstrating that DNA damage in both increases with age. The
researchers also showed an age-related decline in expression of a group of
genes essential for DNA damage repair, including the BRCA genes.

Mouse eggs engineered to express low levels
of DNA repair genes were then exposed to hydrogen peroxide, or bleach. As
expected, higher rates of DNA damage were observed in these eggs when compared
to controls. However, older mouse eggs engineered to over-express BRCA1 were on
par with eggs from younger mice in coping with hydrogen peroxide exposure.

Finally the paper includes studies on both
mice and people with mutations in the BRCA1 and BRCA2 genes. In humans BRCA1
mutations were linked to lower 'ovarian reserve' - a measure of how many
oocytes a woman has in her ovaries - and in mice with lower litter sizes.

BRCA2 mutations did not appear to have an
appreciable effect. However, according to The Scientist, Dr Oktay 'suspects that
the BRCA2 mutation may
have more minor effects on oocyte decline that become apparent later in life'.

In a commentary accompanying the study, Dr
David Keefe of New York University, says that the findings 'provide compelling
new evidence for a new mechanism' explaining why a woman's eggs become
dysfunctional with age.

Dr Oktay says he hopes to apply his
research to ultimately find a treatment to help maintain the efficiency of DNA
repair mechanisms, which would in turn extend a woman's window of fertility. 'Such
a treatment might be able to extend a woman's ability to have children into her
early 50s', he told Bloomberg News.

However, speaking to The Scientist, he added:
'We need to find out why with age the repair efficiency goes down. Then we can
manipulate the whole thing'.