Melina Schuh Since she began her graduate studies in 2004, she has been fascinated by ovarian germ cells, or oocytes. ”[I] “We realized that very little is known about these important cells that are essential for reproduction and the creation of new life,” she said. Now a biochemist at the Max Planck Institute for Interdisciplinary Sciences, Schuh became interested in how oocytes (all formed before birth) can maintain their functionality for decades. We are interested in the factors that may lead to the eventual decline of these poorly studied cells. .
In a recent study, Hsu and her team found that mammalian ovarian cells have very long-lived protein.1 The survey results are natural cell biologyshed light on adaptations that help maintain oocyte damage with minimal damage throughout the reproductive period of female animals and provide clues about the decline in fertility in aging ovaries.
“While the biology of extremely long-lived proteins in aging has been known for some time, this is the first paper to carefully characterize the nature and identity of these proteins in the ovary,” he said. Ray Rayis a reproductive biologist at the University of Missouri School of Medicine but was not involved in the study. Creating new proteins involves the risk of making mistakes, which oocytes cannot afford, he added. “Because at the end of the day, you’re supporting a new life.”
report of long-lived protein complex In oocytes, Xu wondered about the prevalence of this phenomenon and whether protein longevity played a functional role in maintaining these cells.2 To find out how long the proteins could survive in oocytes, Xu and her team fed pregnant female mice a diet containing amino acids containing heavy isotopes of carbon. These mice, along with their pups in the womb, incorporated this heavy element into their proteins. When the animals gave birth, the scientists fed the newborns a diet containing lighter carbon isotopes. This strategy meant that the proteins the pups made before changing their diet contained heavier carbons, while the proteins synthesized later contained lighter carbons.
The researchers then collected oocytes from the puppies, which reached puberty at eight weeks of age. Mass spectrometry analysis of these cells revealed that almost 10 percent of the proteins were produced before the mouse was born. Long-lived proteins belonged to various cellular components such as mitochondria, ribosomes, and chromatin, and were involved in functions such as metabolism and DNA repair.
The ovary is composed of cells other than oocytes, such as stromal cells and membranous cells, which play an important role in fertility. The research team wondered if these cells also contained long-lived proteins. They analyzed proteins from the ovaries of mice up to 15 months old, an old age for mice. Mathematical modeling has shown that more than 10 percent of the proteins have half-lives of more than 100 days, and many remain in the ovaries for most of the animal’s life. By comparison, less than 1% of the proteins in cartilage, brain, and muscle lived this long. These long-lived ovarian proteins have important functions in structures such as mitochondria and the cytoskeleton, and processes such as proteostasis and chromatin maintenance. RNA sequencing revealed that, apart from oocytes, a subset of somatic cells within the ovary also harbor these long-lived proteins.
The researchers then wondered how these proteins could persist for so long. To determine whether altered proteostasis played a role, they tested whether aged oocytes contained aggregates of misfolded proteins. Microscopic examination revealed that such aggregates were absent in aged oocytes. The researchers also confirmed that the activity of the proteasome, a complex that degrades misfolded proteins to maintain protein homeostasis within cells, does not decline with age.
Analysis of protein abundance in the ovary shows that it is rich in antioxidants and chaperones that help protein folding, preventing protein misfolding and protecting against oxidative damage, allowing proteins to remain stable for long periods of time. It was suggested that it be maintained.
To understand the effects of ovarian aging on these long-lived proteins, researchers examined the abundance of the proteins in mouse ovaries at several time points throughout life, from 1 day after birth to 11.5 months. Mass spectrometry reveals that ovarian aging is associated with a decrease in many long-lived proteins. This leads to a massive reorganization of the ovarian protein landscape, ultimately leading to a gradual decline in fertility in mice after 3 months of age.
Xu said finding a long-lived protein in the ovary was not entirely unexpected. “But it was surprising that so many proteins persisted for so long,” she says. Her team began investigating some of these long-lived proteins to understand why they are not degraded more frequently and what functional implications their longevity may have.
“These results are important for understanding the biology of the human ovary and ovarian aging,” Professor Ray said, adding that based on these results it is possible to slow down ovarian aging or improve egg quality. He cautioned against designing medical treatments to do anything. This is primarily because the biology of human ovaries is more complex than that of mice, she explained.
“how [these results] “We still don’t know if it’s directly related to humans,” Xu agreed. But she expects human ovarian proteins to also be long-lived. While this is currently difficult to study in humans, “it would be absolutely exciting if we could one day extend this to humans,” she said.
