How the ovarian reserve is established

Researchers define the epigenetic machinery that governs the establishment and function of the mammalian ovarian reserve, providing molecular insights into female reproductive health and lifespan, in a new study published in Nature Communications.

"In human females over the age of 35, you see a decline in fertility," said the lead researcher of the paper. "Our study may give us the foundation to understand how female fertility is established and maintained at the molecular level and why it declines with age."

When the ovarian reserve is established, all the oocytes in primordial follicles pause their development and can remain in such an arrested state for decades.

"The main question is how can these cells be maintained for decades,?said the researchers.g

Using mouse mutants, the team found that the pausing of this oocyte transition phase was mediated by a group of proteins called the Polycomb Repressive Complex 1 (PRC1).

PRC1 suppresses the development process, called meiosis, that occurs prior to establishing the ovarian reserve, thereby ensuring a proper gene expression program in the ovarian reserve. When the team created mouse mutants with depleted PRC1 machinery, they found that the ovarian reserve could not be established and the cells underwent cell death.

"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," they noted.

According to Namekawa and his colleagues, deficiencies in PRC1 functionality may help explain cases of premature ovarian failure and infertility in humans.

Ref:

Satoshi Namekawa et. al, PRC1-mediated epigenetic programming is required to generate the ovarian reserve, Nature Communications, 10-Aug-2022, DOI: 10.1038/s41467-022-31759-6