Recent Developments in Identifying Genetic Determinants of Premature Ovarian Failure

Abstract

Premature ovarian failure (POF) is defined as cessation of menstruation and associated elevation of gonadotropin levels (FSH >40 IU/l) as a result of decreased ovarian function prior to the age of 40. An estimated 1% of the population is affected before age 40, with 0.1% affected prior to age 30. Although the causes for POF are many, the majority of POF cases have idiopathic etiologies. In an effort to investigate potential mechanisms of the disease, genetic determinants of POF have received particular attention in recent years. Transgenic mouse models have been instrumental in the discovery of novel genetic determinants of gonadal development and failure and have informed research identifying mutations in women with POF. Here, we review recent developments in identifying genetic determinants of POF.

Reductions in the number of mid-sized antral follicles are associated with markers of premature ovarian senescence in dairy cows

“…Two major reasons for the development of POF have been proposed: (1) failure to acquire an adequate number of initial primordial follicles, which normally takes place during fetal life; and (2) excessive clearance of primordial follicles, together with the suppressed activation and further development of primordial follicles (Jagarlamudi et al 2010). The aetiology of most of cases of POF is idiopathic; however, this condition has a heterogenous background (Nelson 2009;De Vos et al 2010) and, in the past decade, an increasing number of genes has been implicated in premature ovarian failure (Goswami and Conway 2005;Skillern and Rajkovic 2008;van Dooren et al 2009;Persani et al 2010;Cordts et al 2011). Light and transmission electron microscopy studies have led to the identification of two POF phenotypes: follicular and afollicular POF ovaries (Haidar et al 1994;Massin et al 2004Massin et al , 2008.…”

RanBPM is essential for mouse spermatogenesis and oogenesis

“…Premature ovarian failure has numerous causes (for reviews, see Jagarlamudi et al, 2010;Skillern and Rajkovic, 2008). The premature ovarian failure observed in RanBPM -/-mice was directly linked to an early depletion of the oocyte pool.…”

Premature Ovarian Insufficiency: Aetiology and Long-Term Consequences

“…1,20,21 It affects around 1-3% of women in the reproductive age below 40 years and around 0.1% in women below 30 years of age. 2,10,18,22,23 Women with POI, around 10-28% experience primary amenorrhea and 4-18% secondary amenorrhea. 10,18 Incidence of spontaneous onset POI has increased due to increasing success rates of cancer treatment in girls and young women.…”