Fibrosis drugs reverse ovarian ageing in mice
Dr Rachel Montgomery
Progress Educational Trust30 June 2022
Ovarian ageing in mice has been shown to be reversible using compounds that target fibrosis and promote mitochondrial health.
Scientists in Australia have discovered that as mice age they show increased levels of ovarian fibrosis, caused by mitochondrial dysfunction, inflammation, and excess collagen accumulation. In turn, these changes stiffen the architecture of the ovaries and impair ovulation – leading to reduced fertility. They suggest that this mechanism may explain why fertility in women can decline in their 30s, long before menopause.
'One challenge we faced was convincing our clinical colleagues that ovarian fibrosis (the excess inflammation and collagen) could actually be preventing egg release from ovaries' said study leader Professor Rebecca Robker from the University of Adelaide, Australia. 'Currently, clinical treatments for triggering ovulation in women involve administering very high doses of hormones to make the egg-containing follicles grow and mature, and the search for new therapies has been all about finding new hormones or treatment protocols to stimulate these follicles.'
The research, published in Science Advances, showed that fibrosis was already widespread in the ovaries of 12-month-old mice (corresponding to about 35 human years), which is considerably earlier than previously thought. Obese mice also had increased levels of ovarian fibrosis and exhibited a loss of fertility comparable to the aged mice.
The researchers found that using drugs to target ovarian fibrosis – including those that improve mitochondrial function and reduce inflammation – improved ovulation rates. This is the first study to identify non-hormonal methods to improve ovarian function, although the findings still need to be replicated in humans.
Reflecting on the results, Professor Robker said 'there is likely to be a treatment for ovarian fibrosis in the foreseeable future' but cautioned that a non-invasive way to diagnose ovarian fibrosis is needed to identify patients who could benefit.
'Women are increasingly wanting to have children later in their reproductive life, and enhancing the function of the ovaries at that time would be valuable,' commented Professor Richard Anderson from the MRC Centre for Reproductive Health at the University of Edinburgh, who was not involved in the study. 'There are lots of questions about whether this [research] might be relevant to women, but we do know that older human ovaries have more collagen, and that this can affect egg development in human ovaries as well as in mice.'
Sources and References
17 June 2022. Science Advances
Female reproductive life span is extended by targeted removal of fibrotic collagen from the mouse ovary
21 June 2022. Lifespan
Targeting fibrosis reverses ovarian ageing in mice
21 June 2022. Bioworld
Ovarian fibrosis-mediated ovulation failure is reversible: study
17 June 2022. Science
Softening tough tissue in aging ovaries may help fight infertility
Reproduced with permission from BioNews, an email and online sources of news, information and comment on assisted reproduction and genetics.