Scientists say findings may help explain cases of premature infertility in humans
Scientists have decoded the biological mechanisms in mice governing the ovary’s capacity to provide eggs, and how it changes with age in a new study. The advance sheds new light on female reproductive health and lifespan.
Fertility is finite in mammalian females, who possess a limited number of fluid-filled sacs, or follicles, in the ovary.
Since birth, as these eventually develop eggs, the “ovarian reserve” decreases with age.
“Despite its fundamental importance, our understanding how the ovarian reserve is established and maintained remains poor,” Satoshi Namekawa, a co-author of the study from the University of California, Davis, said in a statement.
The new study, published in the journal Nature Communications on Wednesday, assessed epigenetic changes that define the process, which are processes that influence how genes work, without altering DNA itself.
“In human females over the age of 35, you see a decline in fertility. 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,” Dr Namekawa said.
When the ovarian reserve is established, researchers say all the undeveloped eggs, or oocytes, in the follicles pause their development and can remain in such an arrested state for decades.
One of the main questions biologists have pondered is how these cells are maintained in this state for decades.
“They cannot divide, they cannot proliferate, they just stay quiescent in the ovaries for decades. How is this possible?” Dr Namekawa said.
In the new research, using mutant mice, researchers found that the pausing of this oocyte transition phase was mediated by a group of proteins called the Polycomb Repressive Complex 1 (PRC1).
When they created mouse mutants with depleted PRC1 machinery, scientists 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,” Dr Namekawa explained.
Scientists suspect deficiencies in PRC1 functionality may help explain cases of premature ovarian failure and infertility in humans.
In future studies, researchers hope to uncover a more detailed mechanism of this process.
“Our study demonstrates a fundamental role for PRC1-mediated gene silencing in female reproductive lifespan, and reveals a critical window of epigenetic programming required to establish ovarian reserve,” they wrote in the study.