Early ovarian folliculogenesis is characterized by the breakdown of germ cell clusters and formation of primordial follicles. The cessation of ovarian function under the age of 40 years results in premature ovarian failure (POF) and is accompanied by amenorrhea, hypoestrogenism and elevated serum gonadotropin concentrations. 1% of all women are affected by POF, and mutations in a few genes, including inhibin? fsh receptor and the LH/choriogonadotropin receptor have been linked to POF. In addition, several germ cell specific genes and downstream transcription factors are thought to play and important role in human oogenesis. NOBOX (newborn ovary homeobox gene), an ooctye-specific homeobox gene, is a critical protein involved in early folliculogenesis. Missense mutations have been shown to cause nonsyndromic ovarian failure by disrupting the NOBOX proteins ability to bind to NOBOX DNA-binding element (NBE), and thereby inhibiting its regulation of Pou5f1 and GDF-9. NOBOX expression in the ovary is oocyte specific, but it shows expression in adult testis and pancreas as well.
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