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ReproUnion supported PhD adds novel insights to the understanding of female reproductive ageing

Oct 12, 2020

The current trend of having children later in life combined with the age-related decrease in the female ability to produce offspring, may explain the declining fertility rate in Denmark and beyond.

Today, we do not fully understand the complex cellular mechanisms involved in the ageing of ovarian follicles. With age women experience a reduction in oocyte functionality, due to an abnormal number of chromosomes. Their ovarian reserve (number of primordial follicles) is also reduced significantly, from several hundred thousand follicles in puberty to below thousand at the time of menopause.

“We need deeper insights about the biology associated with ovarian ageing to provide future strategies for prevention and/or treatments of age-related female infertility. Ultimately, a clinical biomarker for ovarian ageing would enable women to better plan the time for pregnancy – according to their own life preferences in combination with their own biology,” explains Kristina Wendelboe Olsen, who successfully defended her ReproUnion supported PhD on the 25th of September 2020.

In the video above Kristina explains the aim of her PhD project: to describe the DNA methylation profile (epigenetic profile) of the human ovarian follicle cells (mural granulosa cells) with the effect of age and ovarian reserve, and to identify any potential age-related changes in the gene expression of the human oocyte.


Over a 2.5-year period, 211 women donated mural granulosa cells, leukocytes, and oocytes from their treatments at fertility clinics in Denmark and Sweden. Part of the findings were that leukocytes follow the chronological age of the women, while mural granulosa cells have a very young DNA methylation age, when calculated with exciting epigenetic clocks. This result led to the development of the Granulosa Cell clock published in Human Reproduction in May 2020.

“We can only speculate that the function of mural granulosa cells is affected by age, which in turn could explain the age-related decline in oocyte competences seen in women. This knowledge could potentially contribute to developing a future biomarker for the timing of the loss of fertility, thus allowing women to make informed reproductive decisions,” says Kristina and adds a concluding remark: “Collectively, my PhD project enlighten our understanding of the genetic and epigenetic ageing process of the cells of the human ovarian follicle”.

Since the above article was written findings from Kristina’s PhD project have also been published in the article from Fertility and Sterility: Identification of a unique epigentic profile in women with diminished ovarian reserve


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