Stopping the maternal biological clock

Jul 26 2017

Fertility researchers from HMRI’s Pregnancy and Reproduction Program have identified an antioxidant that can potentially halt the ageing process in female eggs and provide a future solution for women who want to fall pregnant at an older age.

PhD student and lead researcher Bettina Mihalas, along with colleagues from the University of Newcastle’s Reproductive Science Group, made the discovery by applying a model commonly used in sperm research to female eggs.

Their findings are reported in the prestigious Nature publication Scientific Reports. Read the full paper here.

“What we found is a link between the deterioration of a certain protein in the female egg, which worsens with age, and its subsequent effect on the ability of chromosomes to separate,” Ms Mihalas said.

“Further to this, we investigated the application of an antioxidant, which we observed to be successful in restoring the integrity of chromosome separation. The results are really encouraging as, with further study, this method could be explored as a possible solution to improving egg quality in mature women.”

The average childbearing age in Australia has risen from 27.7 years in 1987 to 31 years in 2010, while the percentage of first-time mothers aged 35-39 has almost tripled in the past 20 years. The UK, US and Japan have similar trends.

Women present with decreased fertility as their maternal age rises and pregnancy risk also increases. The incidence of chromosome disorders, for example, is approximately 2% for women in their 20s but 35% for those in their 40s and 50% in their 50s.

“Women in developed countries are delaying child bearing to pursue their professional aspirations or ensure they have met the right partner,” Ms Mihalas said. “I’m hopeful that our results will aid the research in this area and prompt further work to facilitate women who embody this trend and are choosing to start a family later in life.”

An increase in what’s known as intra-ovarian ROS (reactive oxygen species) has long been linked to the decline in egg quality associated with maternal ageing, correlating with reduced embryo development and a decrease in live births.

Despite this, co-author and reproductive researcher Professor Brett Nixon says that the way ROS elicits damage to eggs remains largely unexplored.

“With age, you get a marked increase in ROS and decrease in antioxidant defences, so you’ve essentially got a perfect storm,” he explained. “What’s really exciting about our findings is that we’ve been able to identify that ROS targets and hinders the functionality of the tubulin family, which is a key protein responsible for chromosome separation.

“This will be a vital piece of knowledge moving forward with the research, as it paints a better picture of exactly what causes age associated chromosome abnormalities and miscarriage,” Professor Nixon said.

The antioxidant used in the study has benefitted sperm research and young female eggs under the effects of ROS, with researcher Dr Geoffry De Iuliis now keenly interested in exploring antioxidant use in therapeutic treatment.

“If we can develop these antioxidants based on current technology then we’d be in business, but we won’t know the extent of any benefits until we do the science,” he said. “We need the antioxidant to pass through the gut intact, make it to the reproductive system and then see a therapeutic benefit.”

The research team hopes the new findings will enable them to further explore the effects of ROS and various treatments to combat decline in egg quality, in a hope to ultimately provide women more options when considering starting a family.

* Bettina Mihalas, Professor Nixon and Dr De Iuliis are from HMRI’s Pregnancy and Reproduction program. HMRI partners with the University of Newcastle and Hunter New England Health.