Human Disease




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Folliculogenesis consists of three main processes including primordial follicle assembly, follicle development and ovulation (McGee and Hsueh 2000, Vanderhyden 2002, Adhikari and Liu 2009). It is the progression of number of small primordial follicles into large preovulatory follicles that enters the menstrual cycle (DiZerega, Turner et al. 1981, Edson, Nagaraja et al. 2009). Folliculogenesis begins with primordial follicle assembly (during the perinatal period in human, mouse and rat) during which the oocytes that survive the process of germ cell cluster breakdown are individually surrounded with squamous pre-granulosa cells (Baker 1963, Hirshfield 1991, Eppig 2001, Pepling and Spradling 2001, Pepling 2006, Broekmans, Knauff et al. 2007). The recruitment (or the initial growth) of primordial follicles is defined by a dramatic enlargement of the oocyte itself, accompanied by proliferation and differentiation of the surrounding granulosa cells (Faddy and Gosden 1996, Wandji, Srsen et al. 1996, Eppig 2001, Hansen, Knowlton et al. 2008). Ovulation is the last step of folliculogenesis, which involves the breakdown of a mature ovarian follicle to release a fertilizable oocyte (Fathalla 1971, Richards 1980, Wandji, Srsen et al. 1996, Richards, Russell et al. 2002, Rolaki, Drakakis et al. 2005).

The ultimate role of the folliculogenesis, a tightly regulated process that lasts for two to five decades in women, is to produce a healthy egg that will transmit genes to the next generation (Edwards 1965, Richards 1980, Mehlmann 2005, Assou, Anahory et al. 2006, Devoto, Fuentes et al. 2009, Fan, Liu et al. 2009). Inappropriate coordination of these events will result in serious ovarian pathologies such as POF (premature ovarian failure) and PCOS (polycystic ovary syndrome) (Welt 2008, Goodarzi, Dumesic et al. 2011). In humans, POF is defined as an ovarian defect characterized by absence of menarche (primary amenorrhea) or premature depletion of ovarian follicles/arrested folliculogenesis before the age of 40 years (secondary amenorrhea, 25). POF affects ∼1 in 10 000 women by the age of 20 (0.01%), 1 in 1000 women by the age of 30 (0.1%) and 1 in 100 women by the age of 40 (1%, 24). PCOS is another common female endocrine disorder that affects ∼5–10% of women of reproductive age (12–45 years) (Goodarzi, Dumesic et al. 2011). These two diseases are considered to be the leading causes of female subfertility and the most frequent endocrine problems in women of reproductive age (Goodarzi, Dumesic et al. 2011). Currently there are no effective treatments for these ovarian pathologies and in many cases, POF and PCOS are generally diagnosed only when women have already lost their fertility (Welt 2008, Goodarzi, Dumesic et al. 2011).

Although the physiological function of folliculogenesis is well defined, the mechanisms controlling this process are not properly understood. Until recently, the tools available to reproductive biologists to determine the functions of genes involve in mammalian folliculogenesis were based on the study of homologous genes in lower model organisms and the production of genetically modified mice with targeted disruptions of genes of interest (Matzuk and Lamb 2008, Jagarlamudi, Reddy et al. 2010). These studies not only suggested that which molecules may be involved in the folliculogenesis in human but they were also able to highlight specific candidate molecules that can be used as targets for potential drugs used to treat ovarian pathologies (Matzuk and Lamb 2008, Jagarlamudi, Reddy et al. 2010). However, information about the genes/proteins involved is folliculogenesis was scattered across thousands of publications and extraction of relevant functional information from various resources is a significant task. Thus, an integrated database of the existing resources regarding folliculogenesis was urgently required.

By searching literature, we manually collected unique proteins from 23 species with experimentally verified functions during folliculogenesis. This led us to the development of an integrated and searchable database, Follicle Online. We present here the database (Follicle Online) of genes experimentally linked with folliculogenesis (also PCOS and POF). This online service is implemented in PHP + MySQL + JavaScript. Follicle Online can provide potentially orthologous genes for these genes/proteins reported in Follicle Online from seven model organisms, including Homo sapiens, Mus musculus, Rattus norvegicus, Macaca mulatta, Danio rerio, Bos taurus and Gallus gallus. Follicle Online will be regularly updated as soon as new genes/proteins regulating folliculogenesis (also PCOS and POF) will be reported. It possess a comprehensive set of features, which allows users to explore different aspects of functionality of the folliculogenesis genes indexed in Follicle Online and provides important information required for further experimentally or bioinformatics analysis of these genes.

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