Premature ovarian failure: a critical condition in the reproductive potential with various genetic causes

Premature ovarian failure [POF] is identified as a heterogeneous disorder leading to amenorrhea and ovarian failure before the age of 40 years. The first known symptom of the disease is having irregular menstrual periods. The phenotype appearance of POF depends significantly on the variations in hormones. Low levels of gonadal hormones [estrogens and inhibins] and increased level of gonadotropins [luteinizing hormone [LH] and Follicle stimulating hormone [FSH]] [hypergonadotropic amenorrhea] are well documented as causes of POF. There is an association between the failure of germ cell development and complete ovarian failure, and consistently decreased number of germ cells is more likely associated with partial ovarian failure resulting in secondary amenorrhea. A literature review on recent findings about POF and its association with genomic alterations in terms of genes and chromosomes. POF is a complex heterogeneous disorder. Some of POF cases are carriers of a single gene mutation inherited in an autosomal or X-linked manner while a number of patients suffer from a chromosome abnormality like Turner syndrome in mosaic form and manifest secondary amenorrhea associated with ovarian dysgenesis. Among many of the known involved genes in POF development, several are prove to be positively associated to the disease development in different populations. While there is a promising association between X chromosome anomalies and specific gene mutations with POF, genome-wide analysis could prove a powerful tool for identifying the most important candidate genes that influence POF manifestation

Chromosomal abnormalities & oxidative stress in women with premature ovarian failure (POF).

Background & objectives: Premature ovarian failure (POF) is defined as the cessation of ovarian function under the age of 40 yr and is characterized by amenorrhoea, hypoestrogenism and elevated serum gonadotrophin levels. The cause of POF remains undetermined in majority of the cases. This study was aimed to investigate the type and frequency of cytogenetic abnormalities in patients with idiopathic POF and also to study the role of oxidative stress in such cases. Methods: Seventy five women with idiopathic POF were included in this study. Chromosome analysis was done in peripheral blood lymphocytes by conventional GTG banding to identify numerical or structural abnormalities. Cytogenetically normal cases were investigated for reactive oxygen species (ROS) levels in their blood by luminol-chemiluminescence assay. Results: Eighteen chromosomal anomalies were identified in POF patients (24%). Majority of the cases were found to have X-chromosome abnormalities (28%). Overall median ROS range was found to be significantly higher (P<0.01) in POF patients [50480 (120,132966) RLU/min] compared to controls [340 (120,5094) RLU/min]. Among these, 50 per cent of the POF patients had higher ROS levels, 20 per cent had medium elevation and 30 per cent were found to have normal values comparable to controls. Interpretation & conclusions: X-chromosome anomalies were found to be the major contributor of POF. Oxidative stress may be the underlying aetiology in idiopathic premature ovarian failure. Thus the results of this study highlight the role of cytogenetic abnormalities and supraphysiological levels of ROS in causation of idiopathic POF. But the role of oxidative stress needs to be confirmed by other studies on patients from different geographical areas and from different ethnicities.

Falla ovárica prematura: causas genéticas

Presentamos una paciente de 33 años de edad que consulta por amenorrea secundaria causada por una Falla Ovárica Prematura(FOP) secundaria a un Síndrome Turner en mosaico. La FOP definida como amenorrea hipergonadotrópica en pacientes menores de 40 años tiene una incidencia del 2 al 10 por ciento. Es causada por diferentes entidades entre las que encontramos desórdenes autoinmunes, defectos metabólicos y enzimáticos, enfermedades infecciosas, causas iatrogénicas, defectos en las gonadotropinas y causas genéticas. Estas últimas son responsables de FOP especialmente en pacientes menores de 30 años, en las que se justifica la solicitud de cariotipo como parte del estudio. Describimos las características de la disgenesia gonadal, del Síndrome Turner y los elementos funcionales del cromosoma X cuya ausencia altera la función gonadal. También mencionamos los diferentes mosaicos descritos en relación al Síndrome Turner y sus consecuencias en el desarrollo somático y gonadal

Premature ovarian failure: morphological and ultrastructural aspects

Os autores analisaram, através de microscopia de luz e de microscopia eletrônica, os ovários de mulheres com insuficiência ovariana prematura. Observaram que säo constituídos por tecido conjuntivo denso e raros corpos albicantes. Oito dos 10 casos näo apresentavam folículos primordiais; en un caso verificou-se a presença de folículos ovarianos atípicos e, em outro identificou-se corpo lúteo (após estimulaçäo com gonadotrofina exógena). A ultra-estrutura, verificou-se que os fibroblastos achavam-se unidos uns aos outros através de prolongamentos celulares, formando un sincício celular