Females are born with a finite supply of oocytes housed within dormant primordial follicles known as the ovarian reserve (OR). The current gold-standard to quantify the OR requires the removal of the ovary and manual counting via histology. This provides a static snapshot of the ovary, and the OR can only be studied retrospectively in fertility trials. This study aimed to measure the OR in mice at 25 days of age and compare it to breeding performance to see if the number of primordial follicles in early life influences lifetime fertility.
The Figla-CreTg/0-tdTomatofl/0mouse line expresses fluorescent tdTomato in oocytes. The fluorescent output of ovaries from these mice has previously been correlated to the size of the OR. At 25 days old, 27 mice underwent surgery where the ovaries were externalised and imaged by fluorescent microscopy. This was a minimally invasive procedure and mice recovered swiftly post-operation. Through machine learning-assisted image analysis, the number of primordial follicles in each ovary can be counted and the density used to measure the early-life OR in each mouse.
The females were then paired with males, weighed twice weekly, and their pup production was recorded for 9 months. The litter number, litter size, and inter-litter interval are known for each mouse. This is a robust set of lifetime fertility data that shows distinct changes between early and late-life breeding performance and differences in fertility between individuals. Current work is being conducted to optimize the image analysis pipeline to ensure the accuracy of the counts of the OR from the fluorescent images.
To our knowledge, this is the first time that OR has been accurately measured in live animals without biopsy or ovary removal. Work is ongoing to determine if early life OR correlates with lifetime fertility.