Some mouse oocytes that began developing early in life remained in the ovary for a year, spending at least 11 months in a secondary follicle, a structure formed by the cells surrounding the oocyte
Some mouse oocytes that began developing early in life remained in the ovary for a year, spending at least 11 months in a secondary follicle, a structure formed by the cells surrounding the oocyte
On October 8, Nature Aging published a study in which researchers genetically labelled mouse oocytes, immature egg cells that had already left dormancy. After 12 months, 4,17% of the originally labelled oocytes remained in the ovary. Oocytes labelled nine months earlier produced healthy offspring after fertilization.
Female mammals have a finite supply of oocytes. Most oocytes lie dormant within follicles, structures made up of cells that support their development. Once an oocyte leaves dormancy, it begins to grow and progresses through several stages before ovulation. A conventional tissue section captures the ovary at a single moment, so the authors labelled oocytes that had already left dormancy in young mice and tracked the same group of cells month by month.
After two months, 47,97% of the originally labelled oocytes remained; after six months, 15,46% remained; and after a year, 4,17% remained. The authors fertilized oocytes in the laboratory nine months after labelling them. Some embryos reached the blastocyst stage, an early stage before implantation in the uterine wall. Transferred two-cell embryos produced healthy offspring. Natural mating also produced labelled offspring six and nine months after labelling.
Oocytes spent the longest time in secondary follicles. At this stage, several layers of cells surround the oocyte and support its development. Oocytes passed through the primary follicle stage in less than a month, while some spent several weeks to at least 11 months at the secondary follicle stage. During long-term observation, about 80% of labelled oocytes were at this stage. Activated oocytes disappeared more quickly in mice labelled at 10 months of age and in young mice that had one ovary removed. The authors link the rate at which activated oocytes are depleted to the time they spend at the secondary follicle stage.
Long-lived oocytes synthesized less RNA and protein and contained lower levels of proteins involved in metabolism. The authors then examined FURIN, an enzyme that helps process certain proteins into their mature forms. Low FURIN levels were associated with prolonged residence at the secondary follicle stage. When the Furin gene was inactivated in oocytes, follicles remained at the secondary stage for longer. Levels of mature GDF9, a signal sent by the oocyte to surrounding cells, also fell. Adding mature GDF9 to follicles cultured in the laboratory partially restored growth.
In this mouse model, activated oocytes progress toward ovulation at different rates. Some spend months in secondary follicles; FURIN and GDF9 are part of a signalling pathway that regulates this rate.