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

18 February 2013
Appeared in BioNews 693

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'.

SOURCES & REFERENCES
Female Biological Clock Runs Out as Egg Repair Genes Wane
Bloomberg |  14 February 2013
Impairment of BRCA1-Related DNA Double-Strand Break Repair Leads to Ovarian Aging in Mice and Humans
Science Translational Medicine |  13 February 2013
Loss of DNA repair in aging ovaries
EurekAlert! (press release) |  14 February 2013
Why Women’s Eggs Don’t Last
The Scientist |  13 February 2013
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