Light shed on epigenetic maintenance of ovarian reserve

Melinda Van Kerckvoorde

Progress Educational Trust

22 August 2022

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[BioNews, London]

Egg cells are kept in a form of stasis from when they are first formed in the fetus until they mature in adulthood, by a protein which regulates transcription, a new study in mice has shown.

During fetal development the ovarian reserve is formed which contains the early egg cells in the follicles. These cells are put into an arrested state immediately after entering the first phase of meiosis, a type of cell division which produces gametes, and may stay in this state for decades. How this reserve is established and maintained until the eggs 'ripen' has been poorly understood.

'Fertility is supported by these arrested oocytes,' said Professor Satoshi Namekawa, who led the study published in Nature Communications. 'The main question is how can these cells be maintained for decades? It's a big question. They cannot divide, they cannot proliferate, they just stay quiescent in the ovaries for decades. How is this possible?'

The aim of this study was to find out if a dedicated epigenetic mechanism, which regulates which genes can be transcribed, regulates the formation and maintenance of the ovarian reserve in this meiotic state. Researchers looked at the potential role of a polycomb protein called PRC1, which is known to mediate epigenetic control of the genome. They specifically looked at what happened when the activity of that protein was silenced.

When the PCR1 was silenced in genetically modified mice, ovaries were much smaller and contained fewer follicles, which is where the egg cells grow and mature. 'We show that a conditional PRC1 deletion results in rapid depletion of follicles and sterility, said Professor Namekawa. 'These results strongly implicate PRC1 in the critical process of maintaining the epigenome of primordial follicles throughout the protracted arrest that can last up to 50 years in humans'.

Other findings demonstrated that PRC1 modulates the expression of many other genes during the formation of the ovarian reserve in the fetus, for example those involved in DNA repair and metabolic processes.

Professor Namekawa concluded, 'Now that we found that this epigenetic process is key for establishment, the next question is can we uncover a more detailed mechanism of this process?' How can the ovarian reserve be maintained for decades?'.

Finally, the research team hopes that future work will reveal if PRC1 dysfunction during this critical developmental window could explain premature ovarian failure and why human fertility declines with age.

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