The genetic origins of ovarian failure

Premature ovarian failure (POF) is a condition characterized by cessation o f ovarian function before the age of 40. The recent meeting at the National Institute of Child Health and Human Development brought together experts f rom diverse disciplines to share current perspectives on the genetic and ph ysiologic origins of POF, with the idea that insights gained from these stu dies may provide important clues about the regulation of normal ovarian agi ng and perhaps aging processes in general. It was suggested that several mu rine genes, including Zfx, c = kit, and the kit ligand, should be fertile c andidates for investigation of the etiology of POF in human families. The s pecific roles of the human DIA and FMR1 gene products in germ cell developm ent need clarification in murine models, and there are more as yet unidenti fied genes residing on the long arm of the X chromosome that are also impli cated in the regulation of human ovarian function. Genes acting at later st ages of oocyte or ovarian follicle function, such as gonadotropin hormones and receptors, are responsible for POF in some women. POF has been found to be a heterogeneous disorder, the dissection of which offers promising insi ghts into mechanisms governing germ cell origination, migration, and prolif eration, meiotic mechanisms, and factors governing oocyte maturation and su rvival.