The prorenin receptor – a new candidate gene for ovarian dysfunction (#13)
Fertility is a critical component of reproductive health, but the inability to have children affects men and women across the globe. Infertility can lead to distress and depression, as well as discrimination and ostracism. Among the many origins of female infertility, ovarian dysfunction represents a significant burden of disease. Although the function and physiology of the adult ovary has been investigated in great detail, we know very little about the etiology of conditions such as primary premature ovarian failure or polycystic ovarian syndrome. We have identified a new key factor, PRR (prorenin receptor) that is essential for normal ovarian development and function. PRR has been previously characterised as a renin and prorenin receptor and might play a role in blood pressure control through the renin-angiotensin-system. To date, this factor has not been implicated in ovarian function. Using conditional inactivation of the gene in mouse ovaries (PRRKO mice) we demonstrate that the lack of PRR leads to severe ovarian dysfunction. Ovaries of PRRKO mice show a loss of primordial and primary follicles at 1 month of age, and increased apoptosis in secondary follicles. Hyperplasia of CYP11A1 positive stromal cells suggests that PRRKO ovaries may display sex hormone imbalance. This is also suggested by the observation that uteri form PRRKO mice are enlarged, proliferative and inflamed at 1 month of age. Characterisation of this mouse model will not only help understand the etiology and progression of ovarian disease, but will also provide an invaluable tool to investigate potential treatments of ovarian dysfunction.