Disease relevance of POF1

• A human homologue of the Drosophila melanogaster diaphanous gene is disrupted in a patient with premature ovarian failure: evidence for conserved function in oogenesis and implications for human sterility [1].
• It is concluded in this review that POF in association with adrenal autoimmunity and/or Addison's disease (2-10% of the idiopathic POF patients) is indeed an autoimmune disease [2].
• An autoimmune etiology is hypothesized for the POF cases with a concomitant Addison's disease and/or oöphoritis [2].
• A strong argument against an autoimmune pathogenesis of POF in these patients is the nearly absent histological confirmation (the presence of an oöphoritis) in these cases (< 3%) [2].
• Arguments in support of this are: 1) The presence of cellular immune abnormalities in this POF patient group reminiscent of endocrine autoimmune diseases such as IDDM, Graves' disease, and Addison's disease; 2) The more than normal association with IDDM and myasthenia gravis [2].

Psychiatry related information on POF1

• We also identified 89 families without a family history of fragile X or mental retardation, and there were 108 subjects who experienced POF, of which 6.5% had a fragile X premutation [3].
• There were no differences between POF and EM patients and between familial and sporadic cases regarding age at menarche, personal history, gynaecological history, weight, height and diet habits [4].
• Causes of oligomenorrhea and amenorrhea include the relatively common conditions of hyperandrogenism, eating disorders, and exercise-induced amenorrhea, as well as uncommon conditions such as pituitary tumor, gonadal dysgenesis, and premature ovarian failure [5].
• Thorough and accurate medical information on POF, support of others, and spirituality were perceived as helpful in coping [6].
• Shyness, social anxiety, and impaired self-esteem in Turner syndrome and premature ovarian failure [7].

High impact information on POF1

• The discovery of FOXL2 may provide insight into the causes of idiopathic premature ovarian failure, a disease that burdens many infertile couples [8].
• Aromatic hydrocarbon receptor-driven Bax gene expression is required for premature ovarian failure caused by biohazardous environmental chemicals [9].
• Familial premature ovarian failure due to an interstitial deletion of the long arm of the X chromosome [10].
• Premature ovarian failure (POF) is defined as a syndrome characterized by menopause before the age of 40 yr [2].
• Accepting the concept that POF is a heterogenous disorder in which some of the idiopathic forms are based on an abnormal self-recognition by the immune system will lead to new approaches in the treatment of infertility of these patients [2].

Chemical compound and disease context of POF1

• Prenatal exposure to galactose or its metabolites may contribute to the premature ovarian failure characteristic of human galactosemia [11].
• Use of a gonadotropin-releasing hormone analog for protection against premature ovarian failure during cyclophosphamide therapy in women with severe lupus [12].
• CONCLUSION: Determination of selected cytochrome P450 enzyme genotypes may be valuable for predicting the risk of premature ovarian failure in lupus nephritis patients treated with cyclophosphamide [13].
• We examined the association between these genotypes and the following clinical end points: development of premature ovarian failure, end-stage renal disease (ESRD), doubling of serum creatinine level, and achievement of complete renal response [13].
• We suggest that caregivers address the prospect of premature ovarian failure in an open and sensitive manner and emphasize the critical importance of estrogen treatment for feminization and for bone health during the adult years [14].

Biological context of POF1

• Some experimental evidence suggests that these genes might be clustered on the female sex chromosome in the POF1 and POF2 loci [15].
• Premature ovarian failure (POF) is a defect of ovarian development and is characterized by primary or secondary amenorrhea, with elevated levels of serum gonadotropins, or by early menopause [1].
• During a routine prenatal diagnosis we detected a female fetus with an apparent terminal deletion of an X chromosome with a karyotype 46,X,del(X)(q25); the mother, who later underwent premature ovarian failure, had the same Xq deletion [16].
• We propose that the human DIA gene is one of the genes responsible for POF and that it affects the cell divisions that lead to ovarian follicle formation [1].
• In agreement with previous results, these findings suggest that the deletion of a restricted Xq region may be responsible for the POF phenotype [17].

Anatomical context of POF1

• Genes acting at later stages of oocyte or ovarian follicle function, such as gonadotropin hormones and receptors, are responsible for POF in some women [18].
• Oocyte donation and gamete intrafallopian transfer as treatment for premature ovarian failure [19].
• Disruption of POF1B binding to nonmuscle actin filaments is associated with premature ovarian failure [20].
• Immunization of SWXJ female mice with the p215-234 peptide derived from mouse inhibin-alpha activates CD4(+) T cells and induces experimental autoimmune oophoritis with a unique biphasic phenotype characterized by an early stage of enhanced fertility followed by a delayed stage of POF [21].
• Autoantibody to a zona pellucida 3 (ZP3) epitope was found to induce autoimmune ovarian disease (AOD) and premature ovarian failure in neonatal, but not adult, mice [22].

Associations of POF1 with chemical compounds

• In the other 16, with a median age of 36 years (range, 27 to 47), amenorrhea persisted and premature ovarian failure was confirmed by increased serum gonadotrophins and reduced estradiol (E2) concentrations [23].
• This study was performed to evaluate the effectiveness of depot leuprolide acetate, a synthetic gonadotropin-releasing hormone analog (GnRH-a), for protection against POF during CYC therapy [12].
• Patients who were either heterozygous or homozygous for CYP2C19*2 had a significantly lower risk of developing premature ovarian failure (relative risk 0.10; 95% confidence interval 0.02-0.52), after adjustment for age and total number of cyclophosphamide pulses received [13].
• Effect on plasma gonadotropins of cyclic steroid replacement in women with premature ovarian failure [24].
• Ovarian steroidogenesis and serum androgen levels in patients with premature ovarian failure [25].

Physical interactions of POF1

• Relationship between serum estradiol concentration and IGF-I, IGF-II and IGF-binding proteins in patients with premature ovarian failure on short-term estradiol therapy [26].

Other interactions of POF1

• A similar comparison between X-linked entries and a subset of randomly chosen entries from the remaining autosomes also indicates an excess of genes on the X chromosome with one or more mutations affecting sex determination (e.g. DAX1), sexual differentiation (e.g. androgen receptor) or reproduction (e.g. POF1) [27].
• Neither of the two FSHR mutations (566C-->T or1255G-->A) was identified in 40 other Finnish patients with premature ovarian failure [28].
• Studies of FRAXA and FRAXE in women with premature ovarian failure [29].
• A translocation breakpoint 171 kb 5' of the transcription start of FOXL2 causes blepharophimosis/ptosis/epicanthus inversus syndrome (BPES) and associated premature ovarian failure [30].
• FMR1 repeat sizes in the gray zone and high end of the normal range are associated with premature ovarian failure [31].

Analytical, diagnostic and therapeutic context of POF1

• POF has been found to be a heterogeneous disorder, the dissection of which offers promising insights into mechanisms governing germ cell origination, migration, and proliferation, meiotic mechanisms, and factors governing oocyte maturation and survival [18].
• STUDY DESIGN: This was a cross-sectional survey of women with elevated follicle stimulating hormone levels with (premature ovarian failure or early menopause [POF/EM], n = 20) or without (diminished ovarian reserve [DOR], n = 20) amenorrhea [32].
• However, in animal models using ZP immunization, similar follicular depletion and fibrosis (as in the POF women) can be detected [2].
• CONTEXT: In reproductive-age women, one of the common adverse effects of chemotherapy and radiotherapy is premature ovarian failure [33].
• Outcomes were compared with those of two groups undergoing therapy at the same time: (1) women below 40 years of age undergoing oocyte donation for premature ovarian failure (n = 35) and (2) women 40 years of age and above undergoing standard in vitro fertilization and embryo transfer using their own oocytes (n = 57) [34].

References