Premature ovarian failure

Mevalonic aciduria (MVA) and hyperimmunoglobulinemia D syndrome (HIDS) represent the two ends of a clinical spectrum of disease caused by deficiency of mevalonate kinase (MVK), the first committed enzyme of cholesterol biosynthesis. At least 30 patients with MVA and 180 patients with HIDS have been reported worldwide. MVA is characterized by psychomotor retardation, failure to thrive, progressive cerebellar ataxia, dysmorphic features, progressive visual impairment and recurrent febrile crises. The febrile episodes are commonly accompanied by hepatosplenomegaly, lymphadenopathy, abdominal symptoms, arthralgia and skin rashes. Life expectancy is often compromised. In HIDS, only febrile attacks are present, but a subgroup of patients may also develop neurological abnormalities of varying degree such as mental retardation, ataxia, ocular symptoms and epilepsy. A reduced activity of MVK and pathogenic mutations in the MVK gene have been demonstrated as the common genetic basis in both disorders. In MVA, the diagnosis is established by detection of highly elevated levels of mevalonic acid excreted in urine. Increased levels of immunoglobulin D (IgD) and, in most patients of immunoglobulin A (IgA), in combination with enhanced excretion of mevalonic acid provide strong evidence for HIDS. The diagnosis is confirmed by low activity of mevalonate kinase or by demonstration of disease-causing mutations. Genetic counseling should be offered to families at risk. There is no established successful treatment for MVA. Simvastatin, an inhibitor of HMG-CoA reductase, and anakinra have been shown to have beneficial effect in HIDS.     

Premature ovarian failure and tissue engineering

Premature ovarian failure (POF) usually happens former to the age of 40 and affects the female physiological state premenopausal period. In this condition, ovaries stop working long before the expected menopausal time. Of diagnostic symptoms of the disease, one can mention amenorrhea and hypoestrogenism. The cause of POF in most cases is idiopathic; however, cancer therapy may also cause POF. Commonly utilized therapies such as hormone therapy, in-vitro activation, and regenerative medicine are the most well-known treatments for POF. Hence, these therapies may be associated with some complications. The aim of the present study is to discuss the beneficial effects of tissue engineering for fertility rehabilitation in patients with POF as a newly emerging therapy.     

Familial premature ovarian failure.

Premature menopause, ovarian failure younger than 40 years of age, is relatively rare but may preclude childbearing for some women who delay attempts at fertility. We present five kindreds in which a genetic association for premature ovarian failure is strongly suggested. Transmission is either autosomal or (less likely) X-linked dominant in these examples. Chromosomal abnormalities, history of diseases, and toxic chemical or viral exposures previously associated with premature ovarian failure could not be demonstrated in these women. This suggests that these kindreds all represent familial idiopathic premature ovarian failure. These data support the need for menopausal histories on both sides of the family for women seeking to postpone reproduction, as well as for patients with ovarian failure.     

Genetic aspects of premature ovarian failure

Among the causes of premature ovarian failure (POF) two groups of factors are reported: factors which lead to decrease of follicular number and factors which stimulate follicular atresia. In the first group genetic factors are the most important whereas in the second: enzymatic autoimmunological, iatrogenic, toxins and infections are reported. In 1986 familiar POF on the background of long arm of chromosome X deletion was reported. Other chromosomes which are important for normal ovarian function are: chromosome 21 (AIRE gene), chromosome 11 (gene of beta FSH, ATM gene), chromosome 3 (gene responsible for BEPS syndrome) and chromosome 2 (genes of FSH and LH receptors). In this review the role of these genes and results of several epidemiological studies are reported.     

NOBOX homeobox mutation causes premature ovarian failure

NOBOX (newborn ovary homeobox gene) is an oocyte-specific homeobox gene that plays a critical role in early folliculogenesis and represents a candidate gene for nonsyndromic ovarian failure. We investigated whether mutations in the NOBOX gene cause premature ovarian failure (POF). We sequenced the NOBOX gene in 96 white women with POF and discovered seven known single-nucleotide polymorphisms and four novel variations, two of which, p.Arg355His and p.Arg360Gln, cause missense mutations in the homeobox domain. Electrophoretic mobility shift assay (EMSA) confirmed that the missense mutation, p.Arg355His, disrupted NOBOX homeodomain binding to NOBOX DNA-binding element (NBE) and had a dominant negative effect on the binding of wild-type NOBOX to DNA. Our findings demonstrate that NOBOX mutations can cause POF.     

Chemotherapy-induced premature ovarian failure: mechanisms and prevention

Significant advances have been made in the previously unexplored areas of the mechanisms involved in cyclophosphamide (CTX)-induced ovarian toxicity and the protective effects of luteinizing hormone-releasing hormone (LHRH agonists. The structure and function of granulosa cells and oocytes are affected by the chemotherapeutic agent, CTX. Results of experiments in female rats indicate that LHRH agonists may protect the ovaries from the toxic effects of chemotherapy. The protective effect may be related to the inhibition of ovarian mitotic activity during LHRH agonist administration. This inhibition is much more pronounced in female compared to male rats. This may be related to the observed better gonadal protective effects in females compared to males. Further experiments are underway to determine whether similar protective effects occur in female primates.     

Idiopathic premature ovarian failure in 63 young women

BACKGROUND: Premature ovarian failure (POF) in adolescents is defined as primary or secondary amenorrhea associated with high follicle-stimulating hormone (FSH) levels. In normal 46,XX patients, its etiology is most often unknown. We have evaluated the clinical, hormonal and ovarian phenotypes in patients with a normal karyotype who were diagnosed with POF before the age of 18. METHODS: Sixty-three patients were included in this retrospective study. RESULTS: The mean patient age was 20.4 years. The patients presented with three clinical patterns: lack of pubertal development (n = 23), primary amenorrhea with interrupted puberty (n = 18), and secondary amenorrhea with normal puberty (n = 22). Ten patients had a familial history of POF and 6 presented with hypothyroidism. The FSH, estradiol and inhibin B levels were not statistically different in the three clinical groups. Fifty percent of the patients presented small ovaries (length <2 cm) at ultrasonography. The presence of follicles was found at histology in only 7 of the 27 patients who underwent an ovarian biopsy. CONCLUSION: 46,XX patients presenting with early POF rarely presented a specific, identifiable disorder. We discuss the clinical management and different diagnosis strategies to improve our current knowledge of this syndrome.     

X-linked premature ovarian failure: a complex disease

Involvement of the X chromosome in premature ovarian failure was demonstrated by the relatively frequent chromosomal rearrangements in patients, but the requirement of two X chromosomes for ovarian function was quite unexplained until recently. Review of the data on chromosomal rearrangements suggests that several genes along the X chromosomes contribute to ovarian function. In most instances, no single X chromosome gene has a causative role in premature ovarian failure, and the phenotype is likely to derive from the additive effect of X-linked and non-X-linked factors. Recent data on a small group of balanced X-autosome translocations showed that X-linked premature ovarian failure might also be caused by a different mechanism, namely position effect of the X chromosome on non-X-linked genes, and suggest a peculiar organization of the X chromosome during oogenesis.     

Identification of serum biomarkers for premature ovarian failure

Premature ovarian failure (POF) is defined when a female achieves menopause before the age of 40. Although many conditions are known to be causative for POF, the most common one is idiopathic. This study was undertaken to investigate the pathogenesis of POF using proteomic tools. Two-dimensional electrophoresis (2-DE) analysis was performed to screen for proteins differentially expressed in patients with POF. Using liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS), we identified 11 significant proteins differentially expressed in the serum of POF patients: 5 proteins with expression increased more than two folds, 5 proteins with expression decreased more than two folds, and 1 protein expressed specifically in the serum of patients with POF. The results of the 2-DE analysis were further validated by Western blotting and ELISA analyses, which 5 reproductive system-related proteins (Ceruloplasmin, Complement C3, Fibrinogen α, Fibrinogen β, and SHBG) were selected. The different expression levels for these proteins were confirmed and demonstrated the possibility of using them as biomarkers to screen POF. These pre-clinical data provide plausible translational implications for targeting the pathogenesis of POF for each protein.     

Clinico-genetic aspects of the ovarian failure syndrome]

Clinical-genetic examination of 50 patients with menopause praecox syndrome has been performed. The results of the examination show genetic syndrome heterogeneity. Chromosomal and gene mutations take part in the syndrome pathogenesis. Chromosomal abnormalities frequency is 12%. Chromosomal aberrations are presented by different mosaicism types of sex chromosomes. Monogenic syndrome genesis with different inheritance types of the pathologic gene is determined: autosomal-recessive or autosomal-dominant.     

卵巢早衰与肠道菌群关系研究思路探讨

卵巢早衰是一种多因素影响的卵巢功能衰退的疾病,自身免疫在卵巢早衰的病因中所占比例高达10％～30％,目前研究已证实卵巢早衰与Treg、IFN-γ和Th17等多种细胞因子的调节有关.近年来肠道菌群成为国内外的研究热点,其可以影响Treg、IFN-γ、Th17等免疫细胞因子的表达.基于免疫细胞因子在两者之间的作用,笔者大胆...     

Melatonin protects against experimental immune ovarian failure in mice

Experimental immune ovarian failure induced in CBA mice by either administration of xenogenic anti-ovarian antibodies or immunization with allogenic ovarian extracts impaired the meiotic maturation of oocytes and increased apoptosis of follicular cells. Immunization was accompanied with the inflammation and active immune reaction, as shown by the enlargement of regional lymph nodes, the increase of apoptosis in cultured lymph node cells and the increase of band and segmented neutrophil percentage in the blood. Triple injections of melatonin (5 mg/kg of the body weight) an hour before antibodies administration restored the meiotic maturation of oocytes and supported the survival of follicular and lymph node cells. In contrast, melatonin application upon immunization was not effective to prevent the ovary impairment and cell death. It is concluded that melatonin protects against immune ovary failure induced by xenogenic anti-ovarian antibodies.     

Cytogenetic abnormalities in Tunisian women with premature ovarian failure

To identify the distribution of chromosome abnormalities among Tunisian women with premature ovarian failure (POF) referred to the department of Cytogenetic at the Pasteur Institute of Tunis (Tunisia), standard cytogenetic analysis was carried out in a total of 100 women younger than 40 affected with premature ovarian failure. We identified 18 chromosomal abnormalities, including seven X-numerical anomalies in mosaic and non-mosaic state (45,X; 47,XXX), four sex reversal, three X-structural abnormalities (terminal deletion and isochromosomes), one autosomal translocation and one supernumerary marker. The overall prevalence of chromosomal abnormalities was 18% in our cohort. X chromosome aneuploidy was the most frequent aberration. This finding confirms the essential role of X chromosome in ovarian function and underlies the importance of cytogenetic investigations in the routine management of POF.     

Premature labour

Prematurity is by far the commonest cause of neonatal morbidity and mortality. The management of premature labour is empirical because little is understood about the mechanism of labour. Effective uterine relaxant drugs have an important, albeit minor role. Phototherapy has reduced the complications of neonatal hyperbilirubinemia, and the beneficial effect of antepartum corticosteroid therapy in minimizing the risk of respiratory distress syndrome is now convincing. Prophylactic antibiotic therapy in premature rupture of the membranes does not alter perinatal mortality, although postpartum maternal morbidity is reduced. The introduction of neonatal intensive care units has improved the survival rate of premature infants. Sound clinical judgement remains the mainstay in the management of premature labour.