Systematic discovery and classification of ovarian fertility factors.

Female infertility syndromes are among the most prevalent chronic health disorders in women, but their molecular basis remains unknown because of the complexity of oogenesis and uncertainty regarding the number and identity of ovarian factors controlling the assembly, preservation, and maturation of ovarian follicles. To systematically discover such ovarian fertility factors en masse, we employed a mouse model (Foxo3), where follicles are assembled normally but are then synchronously activated. Gene expression profiling of mutant and normal ovaries led to the identification a surprisingly large set of ovarian factors. The set included the vast majority of known ovarian factors, many of which when mutated produce female sterility phenotypes, but most were novel. Subsequent analyses revealed novel classes of ovarian factors and significant overrpresentation on the X chromosome, among other insights into the general properties of oogenesis genes and their patterns of expression.

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Gallardo TD, John GB, Shirley L, Contreras CM, Akbay EA, Haynie JM, Ward SE, Shidler MJ, Castrillon DH