Ovarian differentiation and gonadal failure

Abstract

Ovarian failure can result from several different genetic mechanisms-X chromosomal abnormalities, autosomal recessive genes causing various types of XX gonadal dysgenesis, and autosomal dominant genes. The number and precise location of loci on the X are still under investigation, but it is clear that, in aggregate, these genes are responsible for ovarian maintenance, given that monosomy X shows germ cells that undergo accelerated atresia. Despite recent hypotheses, at present there is no evidence for a gene directing primary ovarian differentiation; this process may be constitutive. Phenotypic/karyotypic correlation and limited molecular confirmation have long shown that proximal Xp and proximal Xq contain regions of the most importance to ovarian maintenance. Terminal deletions at Xp11 result in 50% primary amenorrhea and 50% premature ovarian failure or fertility. Deletions at Xq13 usually produce primary amenorrhea. Terminal deletions nearer the telomeres on either Xp of Xq bring about premature ovarian failure more often than complete ovarian failure. The X-linked zinc finger gene (ZFX) and diaphanous 2 Drosophila homologue (DIAPH2) are the only candidate genes for ovarian maintenance that map to the X chromosome. Additional, as yet unidentified, genes along the X chromosome must be involved. The search for these genes in humans is hampered by the lack of candidate genes that map to the X chromosome, the scarcity of patients with fortuitous autosomal translocations, and small pedigrees, which hinder mapping of the loci. In addition, difficulties with human germ cell research also make it challenging to dissect genes important to ovarian development. Autosomal genes also are involved in ovarian differentiation and gonadal failure. Follicle-stimulating hormone receptor and ataxia telangiectasia are examples of autosomal genes known to cause human ovarian failure. Transgenic mouse models point to many other candidate autosomal genes, and sequencing of the human homologues in affected women should lead to the discovery of new genes responsible for human ovarian failure. Identification, functional analysis, and mapping of novel genes specifically expressed in the ovary of mice and women eventually should lead to fruitful dissection of essential genes in mammalian ovarian development and maintenance.

Intrauterine death in singleton pregnancies with trisomy 21, 18, 13 and monosomy X

“…26,29,[45][46][47][66][67][68][69][70] For the Turner syndrome, there is a variable phenotypic expression, varying greatly in the prognosis, from a more subtle, form whose diagnosis is postnatal and causes short stature, infertility and higher frequency of aortic coarctation, up to more serious forms, with morphological abnormalities that allow prenatal diagnosis and evolve with high intrauterine mortality. 30,[71][72][73][74] The main ultrasound findings described in the literature are cystic hygroma and fetal hydrops, which in this sample were present in 55% (17 of 31) and 77% (24 of 31) of fetuses with the 45X karyotype. In this series, intrauterine mortality was 84% (26 of 31), while in the medical literature this rate ranges from 20 to 82%.…”

Falência ovariana precoce associada a deleção no braço longo do cromossomo: relato de dois casos e revisão da literatura

“…Com deleções mais distais (Xp21) do braço curto, as alterações fenotípicas são geralmente leves, apesar de infertilidade e amenorréia secundária serem comuns. A maioria das pacientes com deleções Xp são de baixa estatura, independente da sua função ovariana, indicando a presença de outros genes determinantes da estatura nestas regiões [14][15][16] . As deleções do braço longo (Xq) usualmente causam falência ovariana quando envolvem a chamada região crítica (Xq13-q26).…”

“…As deleções do braço longo (Xq) usualmente causam falência ovariana quando envolvem a chamada região crítica (Xq13-q26). Apesar de a quase totalidade das pacientes com deleções nesta região terem falência ovariana, algumas exceções foram relatadas 16 . Similarmente às deleções do braço curto, as deleções proximais (Xq13) são usualmente mais graves.…”

Falência ovariana prematura: aspectos atuais

“…A diferenciação ovariana necessita da presença de apenas um X, embora seja imprescindível a presença dos genes do segundo X para a manutenção da função ovariana (9). Assim, a associação da FOP com alterações relacionadas ao cromossomo X reforça a hipótese da necessidade de dois X intactos para o desenvolvimento normal do folículo.…”

“…(2003), sendo relatadas como formas esporádicas de comprometimento (11). As deleções comprometem mais comumente o braço curto do cromossomo X, em especial a região Xq13-25, levando à perda de pareamento e atresia dos oócitos (9).…”