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'Rubber band' protein blamed for falling female fertility with age

25 November 2019
Appeared in BioNews 1025

Decreased fertility and increased risk of miscarriages in older women is linked to a protein involved in egg cell division, scientists say.

The study – a collaboration between the Max Planck Institute in Göttingen, Germany, and Bourn Hall Clinic in Cambridge – showed that the protein named cohesin decays with age, increasing the likelihood of errors during cell division and therefore the incidence of miscarriages in older women. According to the NHS, around one in eight pregnancies will end in miscarriage, with higher occurrence among women aged 35 or older.

'In a 40-year-old woman, you will have 40-year-old eggs, as they are first formed in the embryo when they develop. It already has all its chromosomes then,' said senior study author Dr Melina Schuh from the Max Planck Institute. 'What we found is that the chromosomes are falling apart when women get older.'

Egg production comprises in two stages: the first takes place during embryonic development, and gives rise to oocytes (immature eggs). Girls are born with all the oocytes they will ever have. The second stage takes place as part of a woman's cycle and produces a mature egg suitable for fertilisation.

The study, published in Current Biology, showed that the chromosome instability is caused by the decrease of an essential protein complex called cohesin, which stabilises DNA through wrapping around specific areas like a tight rubber ring. This is particularly important during a cell division process occurring before egg fertilisation, called meiosis, which halves the number of chromosomes from 46 to 23 per egg cell. For this, a cellular machinery, the spindle apparatus, pulls one copy of each chromosome pair to two opposite poles inside the cell by binding DNA-dense regions, called kinetochores.

'The kinetochores play a central role in chromosome distribution: The spindle fibres pull on them for numerous hours as the chromosomes become sorted and arranged on the spindle. They are therefore exposed to very strong forces,' Dr Schuh explained. 'We wanted to know whether anything changes in or around this anchor point due to age.'

Dr Schuh and her team showed that the lower amount of cohesin in older cells decreases the stability and integrity of kinetochores, an effect which could be reproduced in younger egg cells when artificially reducing the amount of cellular cohesin. Increased faulty binding by the spindle fibres therefore could lead to abnormal numbers of chromosomes per cell, known as aneuploidy.

Unfertilised eggs unsuitable for use in IVF were donated anonymously by patients at Bourn Hall Clinic in Cambridge, and the Kinderwunschzentrum Göttingen, for use in the study.

'Recurrent miscarriage is one of the most heart-breaking experiences,' said co-author Martyn Blayney from the Bourn Hall Clinic. 'We are committed to supporting research that will enable us to better understand the complex workings of the egg and help more people to achieve their dream of a family.'

SOURCES & REFERENCES
Meiotic Kinetochores Fragment into Multiple Lobes upon Cohesin Loss in Aging Eggs
Current Biology |  18 November 2019
Why egg cells become error-prone with age
Max Planck Institute for Biophysical Chemistry |  31 October 2019
Why female fertility declines with age: Scientists blame the decay of a protein that acts like a 'rubber-band' inside eggs
Mail Online |  20 November 2019
Why female fertility declines with age: Scientists find decay of a protein is likely to blame
Herald Publicist |  20 November 2019
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