A three-dimensional map of aging mouse ovaries found that about 14% of oocytes are beginning to grow in every age group
A three-dimensional map of aging mouse ovaries found that about 14% of oocytes are beginning to grow in every age group
On August 12, Nature Aging published an article containing three-dimensional images of 101 ovaries from mice aged 5 to 60 weeks. The team identified more than 85 thousand oocytes, which are immature egg cells, and determined the growth stage of each one.
The ovarian reserve is the pool of immature egg cells held within follicles, which are small structures composed of supporting cells. Some follicles remain dormant, while others begin to grow. The oocyte then either undergoes ovulation or is lost when the follicle degenerates through atresia. The size of the reserve therefore depends both on how many follicles leave dormancy and on how many are lost during later stages.
The authors rendered whole ovaries transparent, labeled the oocytes, and imaged each organ with a light-sheet microscope. This microscope illuminates the tissue with a thin sheet of light and produces a three-dimensional image of the entire organ. A 2015 study had already counted follicles throughout the entire mouse ovary. The new article added a series of age groups and software that automatically detected oocytes in the images. In five control ovaries, the automated annotations agreed with manual annotations in 95,3% of cases, rising to 96,7% after a minor correction.
In a June spatial map of the aging mouse ovary, another group found that old mice that were still cycling showed disrupted transitions of follicles and corpora lutea, the temporary structures formed after ovulation, into the required cellular states. The new study addresses a different question: how many oocytes pass through each stage across the entire organ.
In the main series of 56 genetically identical mice, the total number of oocytes declined by more than tenfold with age. About 14% of all oocytes were transitioning from dormancy to growth in every age group studied. Recently activated oocytes were more common in regions of the ovary where dormant oocytes were packed more densely. The authors interpret this constant proportion and spatial association as evidence that ovarian tissue maintains a stable proportion of recently activated follicles.
The authors also divided oocyte development into four stages and compared the age-specific counts with a model of transitions between them. According to the model, about 2,5% of dormant oocytes leave dormancy each week, while most losses occur during the antral stage, when a fluid-filled cavity forms within the follicle. At this stage, the model combines two possible outcomes: ovulation and atresia.
This atlas provides measurements for future experiments, including the number of follicles at each stage and their transitions between stages throughout the entire ovary.