Abstract
In most cases of primary ovarian insufficiency (POI), the cause of the depletion of ovarian follicles is unknown. Fanconi anemia (FA) proteins are known to play important roles in follicular development. Using random insertional mutagenesis with a lentiviral transgene, we identified a family with reduced fertility in the homozygous transgenic mice. We identified the integration site and found that the lentivirus had integrated into intron 8 of the Fanconi E gene (Fance). By RT-PCR and in situ hybridization, we found that Fance transcript levels were significantly reduced. The Fance homozygous mutant mice were assayed for changes in ovarian development, follicle numbers and estrous cycle. Ovarian dysplasias and a severe lack of follicles were seen in the mutant mice. In addition, the estrous cycle was disrupted in adult females. Our results suggest that POI has been induced by the Fance mutation in this new mouse model.
Highlights
Healthy ovarian function is vital for reproductive success and for general health in women
Our results show that the Fanconi E gene (Fance) mutant mice provide a new animal model of primary ovarian insufficiency (POI)
We found no differences between the wild-type Fance+/+ and the heterozygous Fance+/- mice
Summary
Healthy ovarian function is vital for reproductive success and for general health in women. Primary ovarian insufficiency (POI) is a type of ovarian dysfunction that results in premature menopause, usually at less than 40 years of age [1, 2]. Some tests of ovarian reserve have been developed, such as measurement of hormone levels, follicle count by transvaginal ultrasound, and laparoscopic biopsy of the ovarian cortex [2]. The information from these tests is limited. The clinical results show that normal ovarian function requires the presence of a sufficient number of primordial follicles. The intial pool of primordial oocytes is generated by rapid proliferation of primordial germ cells. Accurate repair of any DNA damage that occurs during this rapid proliferation is essential to protect
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