Endocrine Abstracts

Primary Ovarian Insufficiency (POI) is an ovarian defect characterized by the premature depletion of ovarian follicles before 40 years and represents one major cause of female infertility. POI is a heterogeneous disease but, despite its idiopathic origin in most of patients, there is a strong genetic evidence, in particular for X chromosome-linked defects. BMP15 gene maps to Xp11.2 within a Turner locus critical for ovarian function and mutations in this gene have been found i...

The pathogenesis of premature ovarian failure (POF) is largely unknown. However, the evidence of a frequent familiarity for the anticipation of menopause among POF women supports the concept of a strong genetic component at the origin of POF. This is further supported by the findings of several candidate genes and by data coming from natural and experimental animal models. On these bases, several groups are involved in the search for markers able to predict the risk of POF. Th...

The X-linked genes accounting for the determination of the ovarian function are still undefined. In the last few years, a large interest has been dedicated to the BMP15 gene. BMP15 gene encodes for a TGFβ-like growth factor of oocyte origin with a critical role in female fertility in mammals and several other species. This gene maps to a locus on the short arm of X chromosome were locates several traits of TS, including ovarian failure. Several missense variations have be...

The oocyte-derived growth and differentiation paracrine factor BMP15 has emerged as an essential regulator of the ovarian folliculogenesis, from evidences in animal models (knockout mice and sheeps with naturally occurring mutations) and humans. Indeed, several BMP15 mutations have been identified in association with primary ovarian insufficiency (POI), a heterogeneous and frequent fertility disorder characterized by the premature depletion of ovarian follicles in women <4...

The ovarian reserve naturally declines with age, however, 1–2% of women before 40 years experiences a premature exhaustion of the ovarian function and suffers from a fertility defect named Primary Ovarian Insufficiency (POI). The genetic origin of POI is well established and strongly supported by multiple reports of familial cases. To date, thanks to the candidate gene-discovery approach, few X-linked and autosomal genes have been associated to POI onset, but most of 46,X...

Primary ovarian insufficiency (POI) is a highly heterogeneous condition defined by the occurrence of amenorrhoea, hypoestrogenism and hypergonadotropinism in women under 40. POI onset can be triggered by multiple factors, such as iatrogenic events, environmental conditions, autoimmunity or genetic alterations. When the ovarian insufficiency occurs as a consequence of either chromosomal or genetic alterations, it can be associated with other congenital abnormalities and classif...

Primary ovarian insufficiency (POI) is one of the major causes of female infertility, affecting about 3.7% of women before the age of 40. POI is associated with the premature loss of ovarian function and can manifest with primary amenorrhea (PA) or post-pubertal secondary amenorrhea (SA), with elevated gonadotropins and hypoestrogenism. Several evidence established a clear genetic component to POI, albeit heterogeneous. In search of novel causative genes, we screened 64 POI pa...

BMP15 is a TGFβ-like oocyte-derived growth factor involved in ovarian folliculogenesis as a critical regulator of many granulosa cell processes. BMP15 is synthesized as a pro-protein which dimerizes and then is processed in the bioactive mature domain and a large prodomain. The proregion has an important role in the BMP15 processing by driving the dimerization and secretion of the active mature dimers. Since several mutations in the BMP15 gene have been found with differe...

Primary ovarian insufficiency (POI) is a critical fertility defect characterized by a progressive and silent impairment of the follicular reserve. POI aetiology is heterogeneous and largely unknown, but a maternal inheritance often characterizes idiopathic forms. Therefore, we hypothesized a possible involvement of a mitochondrial defect in the pathogenesis of this disease since mitochondrial biogenesis and bioenergetics play an essential role in ovarian folliculogenesis. Our ...

Spontaneous puberty occurs in a subset of Turner syndrome (TS) patients with significant 45,X/46,XX mosaicism. This observation leads to the belief that haploinsufficiency of still unidentified genes on the X chromosome is the cause of the accelerated follicle atresia in TS. Examination of particular X chromosome rearrangements/deletions led to the identification of 2 Xq and 1 Xp loci associated to the ovarian defect in TS. The availability of new generation genetic and cytoge...