Scientists have made a major step towards understanding why older women are more likely to produce abnormal eggs, increasing the risk of infertility, miscarriage and birth defects such as Down's Syndrome.
While researchers have long known that women having babies in their late 30s and 40s posed an increased risk of disability due to eggs containing the wrong number of chromosomes, the underlying cause has not been known.
Research by Newcastle University has shed new light on why this happens.
The key is declining levels of proteins called Cohesins, which hold chromosomes together by entrapping them in a ring. This is essential for chromosomes to split evenly when cells divide.
By tracking chromosomes during division in the egg, the Newcastle team found that the reduced Cohesin in eggs from older females resulted in some chromosomes becoming trapped and being unable to divide properly.
Eggs that are defective in this way may fail to develop resulting in infertility, or they may give rise to a pregnancy with a high risk of miscarriage, or to the birth of a baby with Down's Syndrome.
Dr Herbert, the lead researcher, said: "Reproductive fitness in women declines dramatically from the mid-30s onwards. Our findings point to Cohesin being a major culprit in this."
"Cohesin levels were very much reduced in eggs from older mice and the chromosomes underwent a very messy division resulting in the wrong number of chromosomes being retained in the egg."
She said further research would be carried out to see why Cohesin was lost with age.
"If we can understand this, we will be in a better position to know if there is any possibility of developing interventions to help reduce Cohesin loss," she said.
"Undoubtedly, the best way for women to avoid this problem is to have their children earlier."