Ovarian ageing may be associated with mitochondrial dysfunction

Women’s delay becoming mothers due to demographic and socioeconomic factors, is a topic of maximum interest now in reproductive medicine, as ovarian ageing is becoming an increasingly common cause of infertility. With age, eggs decrease in quality and quantity, often leading to reproductive problems.

In this context, Prof. Emre Seli has presented at the 9^th IVIRMA Congress a study exploring the role of mitochondrial dysfunction in ovarian ageing and possible ways to exploit mitochondrial mechanisms to slow down or reverse age-related changes in the female genital glands responsible for making reproductive cells.

Role of mitochondria

Dr. Seli is convinced of the role of mitochondria on reproductive ageing. “Mitochondria are very special and important organelles that play a key role in cell metabolism. In addition, they have their own mitochondrial DNA and have long been implicated in somatic ageing. Scientists initially worked from the hypothesis that mitochondrial DNA would undergo mutations over time. This would make the production of proteins derived from mitochondrial DNA less efficient. Once the cell lost its ability to generate energy effectively, it would age faster”.

This hypothesis has been supported by animal models; however it is generally not a common cause of somatic cell ageing in humans.

“Since then, many other theories have emerged about how mitochondria may affect cell health and ageing. Some suggest that problems with mitochondrial fusion or problems arising from mitochondrial stress could accelerate ageing. By fusion we mean that mitochondria join or fuse. In fact, this scenario was observed in animal tests, leading to accelerated ovarian ageing and impaired reserve”, explained Dr Seli.

New line of research leaded by IVI

There is no solution at present to the mitochondria-linked acceleration of ageing. However, IVI is leading a line of research that could provide an alternative.

“Similarly, we have used mitochondria replacement. We have taken autologous mitochondria from the patient’s stem cells. We have inserted them into the source with the aim of potential rejuvenation. However, a study by IVI Valencia showed that this approach is not yet useful”, described Dr Seli.

In addition, mitochondria have been used as diagnostic tools by measuring the number of copies of mitochondrial DNA as a predictor of embryo health and viability.

Reversal of ovarian ageing through ovarian reactivation

Approximately 1 in every 100 women under the age of 40 suffers from premature ovarian insufficiency (POI). That is why Ovarian Ageing is one of the topics of recent interest in the reproductive field. Women suffering from this condition can’t conceive a baby with their own eggs and have to resort to oocyte donation.

According to this situation, Professor Antonio Pellicer, President and CEO of IVI, has presented a study presented at this Congress on Ovarian Reactivation, a viable and effective option for these patients that gains importance.

“In recent years our research group has focused on developing new alternatives for patients with diminished ovarian reserve, whose only option was egg donation. Our previous studies show that autologous ovarian stem cell transplantation had been able to optimise the growth of existing follicles, allowing pregnancies and births of babies in low responders with very poor prognosis”, explained Prof. Pellicer.

New experimental study developed by IVI

IVI has developed an experimental study to test the ability of different factors secreted from stem cells to reactivate the ovaries, in an effort to design a more efficient but also less invasive technique.

 “We also tested other factors contained within platelets, which are the basis of the PRP (Platelet Rich Plasma) treatment for women with ovarian insufficiency. In this study we observed that different sources of plasma, stem cell factors or umbilical cord blood plasma were able to induce different degrees of local ovarian vascularisation, cell proliferation, reducing apoptosis and finally promoting follicular growth in mice with damaged ovaries”, concluded Prof. Pellicer.