Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0021359 (infertility)
 26,075 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

BACKGROUND: Spontaneous premature ovarian failure presents most commonly with secondary amenorrhea. Young women with the disorder are infertile and experience the symptoms and sequelae of estrogen deficiency. The mechanisms that give rise to spontaneous premature ovarian failure are largely unknown, but many reports suggest a genetic mechanism in some cases. The small family size associated with infertility makes genetic linkage analysis studies extremely difficult. Another approach that has proven successful has been to examine candidate genes based on known genetic phenotypes in other species. Studies in mice have demonstrated that c-kit, a transmembrane tyrosine kinase receptor, plays a critical role in gametogenesis. Here we test the hypothesis that human KIT mutations might be a cause of spontaneous premature ovarian failure. METHODS AND RESULTS: We examined 42 women with spontaneous premature ovarian failure and found partial X monosomy in two of them. In the remaining 40 women with known 46,XX spontaneous premature ovarian failure we evaluated the entire coding region of the KIT gene. We did this using polymerase chain reaction based single-stranded conformational polymorphism analysis and DNA sequencing. We did not identify a single mutation that would alter the amino acid sequence of the c-KIT protein in any of 40 patients (upper 95% confidence limit is 7.2%). We found one silent mutation at codon 798 and two intronic polymorphisms. CONCLUSION: Mutations in the coding regions of the KIT gene appear not to be a common cause of 46,XX spontaneous premature ovarian failure in North American women.
 ...
PMID:Investigation of KIT gene mutations in women with 46,XX spontaneous premature ovarian failure. 1215 2

Oocyte donation is an effective solution for treating infertile women whose ovaries are non-functional. This infertility condition is known as premature ovarian failure and is most commonly caused by genetic or autoimmune diseases, chemo- or radiotherapy, severe endometriosis and ovarian cancer. Oocyte donation also benefits those women who have functional ovaries yet respond poorly to ovarian hyperstimulation for in vitro fertilisation. Not only does oocyte donation provide healthy oocytes to infertile women, it also allows any genetic diseases of the recipient to be avoided. The process is simple beginning with ovarian hormonal stimulation of the donor followed by trans-vaginal oocyte retrieval. The mature oocytes are then fertilised with the sperm of the recipient's partner and the resulting embryo is transferred to the uterus two to five days later. Careful counselling of all parties involved is necessary before commencing treatment. International experience using oocyte donation has been excellent revealing normal, healthy relationships between the children and their families. Until now, oocyte donation has been illegal in Sweden, yet on 25th April 2002 the Swedish Parliament accepted a change in the law regarding assisted reproduction. According to this new law, oocyte donation will be permitted in Sweden from the beginning of January 2003 providing new hope for infertile couples.
 ...
PMID:[Oocyte donation to be legalized in Sweden. Excellent results reported from other countries]. 1219 31

The bioactive sphingolipid metabolite sphingosine-1-phosphate (S1P), formed by activation of sphingosine kinase in response to diverse stimuli, is an important lipid mediator that has novel dual actions - both inside and outside of cells. S1P is the ligand for a family of five G protein-coupled receptors. Activation of these GPCRs by S1P or dihydro-S1P regulates diverse processes, including cell migration, angiogenesis, vascular maturation, heart development, and neurite retraction. There is also abundant evidence that S1P can function as a second messenger important for regulation of calcium homeostasis, cell growth, and suppression of apoptosis. In many cases, the intracellular level of S1P and ceramide, another important sphingolipid metabolite associated with cell death and cell growth arrest, coordinately determine cell fate. Changes in S1P and ceramide have been implicated in a number of pathological conditions in which apoptosis plays an important role. Importantly, radiation-induced oocyte loss in adult female mice, the event that drives premature ovarian failure and infertility in female cancer patients, was completely prevented by in vivo therapy with S1P. Understanding the biosynthesis, metabolism and functions of S1P can uncover new targets for the pharmaceutical and therapeutic applications of S1P.
 ...
PMID:Sphingosine 1-phosphate as a therapeutic agent. 1220 Jun 69

Of 410 cases of spontaneous or induced abortion in the first or second trimester that were followed up, 95 were infertile. 18 of these had amenorrhea and 12 had oligomenorrhea. Amenorrhea and oligorrhea were more prevalent among the women who were over 31. Amenorrhea, oligomenorrhea, and infertility were more frequent after spontaneous than after induced abortion. Asymptomatic tubal block resulting from reflux of blood from the uterus into the fallopian tube after spontaneous abortion could have been responsible in a number of other cases. Definite causal link with abortion could not be established in any of the other cases of infertility without amenorrhea or oligorrhea. Amenorrhea following abortion was most often due to an endocrinal or mechanical defect (often uterine synechiae). Partial pituitary necrosis, premature ovarian failure, and endometrial tuberculosis were other postabortal causes of amenorrhea and oligomenorrhea.
 ...
PMID:Infertility and amenorrhoea following abortions. 1225 18

Detection of specific autoantibodies remains the most practical clinical and research marker of autoimmune disease. The lack of consensus on ovary specific antibodies as a marker for ovarian autoimmunity has clinical and research consequences. The objective of this review is to summarize the evidence for ovarian autoimmunity and the detection of ovary specific autoantibodies in humans. Evidence favors the presence of an autoimmune disease of the ovary. Ovarian autoantibodies are associated primarily with premature ovarian failure (POF) and unexplained infertility. Variations in detection of ovarian autoantibodies are likely to be due to study design elements such as antibody test format, antigen preparation, and criteria for study and comparison groups. In addition, multiple targets appear to be involved in ovarian autoimmunity including ovarian cellular elements and oocyte related antigens. Many studies only assess one target antigen, leaving individuals with ovarian autoimmunity unidentified. The next most significant advance in characterizing ovarian autoimmunity will be definitive identification of the specific antigens and development of standardized tests based on use of specific antigens.
 ...
PMID:Ovarian autoimmune disease and ovarian autoantibodies. 1239 92

Up to now, the identification of gene mutations causing infertility in humans remains poorly investigated. Temporal progression through meiosis and meiosis specific genes had been extensively characterized in yeast. Recently some mammalian homologous were found. The molecular mechanisms regulating entry into and progression through meiosis in mammals are still unknown. However, disruption of some meiotic genes in mouse showed an essential role of them in meiotic chromosome synapsis and gametogenesis. Moreover, the phenotype of gonads in null mutant mice for some meiotic genes (failure to initiate or blockage in meiosis, lack of gametes or small size of gonads...) could be strikingly similar to clinical observations found in human infertility. The aim of this study was to identify putative mutations in 5 meiotic genes of several clinically well-characterized patients who present unexplained infertility (normal karyotype, women with premature ovarian failure, men with azospermia and without Y micro-deletion). For this purpose, the exons of these 5 genes (DMC1, SPO11, MSH4, MSH5, CCNA1) were all amplified by PCR with specific primers and each amplified-exon was sequenced. Sequences were aligned in comparison to the human corresponding gene available in Genbank. Many heterozygous mutations were found in different genes. Two homozygous mutations were found in MSH4 and DMC1 genes in a young man presenting a testis vanishing syndrome and a woman presenting a premature ovarian failure, respectively. Consequences of such mutations will be examined and verified in model organisms (yeast, mouse) to check the relevance of the mutations in clinical setting.
 ...
PMID:[Human infertility: meiotic genes as potential candidates]. 1247 91

Premature ovarian failure and infertility are well-known side-effects observed in young girls and reproductive-age women treated for cancer. Although the need for tumor eradication in these patients is clear, the long-term consequences of chemotherapy and radiation on non-target tissues, such as the ovaries where large numbers of germ cells (oocytes) are also killed off, are substantial. Unfortunately, the mechanism mediating the undesirable toxicity of cancer therapies in the female gonads has only recently been explored. Nevertheless, some important insights into the role of ceramide and sphingosine-1-phosphate (S1P) as a mediator and suppressor, respectively, of cancer therapy-induced oocyte apoptosis have emerged over the past few years. Such findings are exciting in that a better understanding of the crime--how radiation and chemotherapy kill off this irreplaceable population of innocent cells in the ovaries--may finally allow for the development of novel lipid-based strategies to combat infertility and premature menopause in female cancer patients.
 ...
PMID:Sphingolipids, apoptosis, cancer treatments and the ovary: investigating a crime against female fertility. 1253 46

Foxo transcription factors have been implicated in diverse biological processes, including metabolism, cellular stress responses, and aging. Here, we show that Foxo3a-/- female mice exhibit a distinctive ovarian phenotype of global follicular activation leading to oocyte death, early depletion of functional ovarian follicles, and secondary infertility. Foxo3a thus functions at the earliest stages of follicular growth as a suppressor of follicular activation. In addition to providing a molecular entry point for studying the regulation of follicular growth, these results raise the possibility that accelerated follicular initiation plays a role in premature ovarian failure, a common cause of infertility and premature aging in women.
 ...
PMID:Suppression of ovarian follicle activation in mice by the transcription factor Foxo3a. 1285 9

Inactivating mutations of the FSH receptor have been described in rare cases of premature ovarian failure. Only one mutation was associated with a complete phenotype, including delayed puberty, primary amenorrhea, and small ovaries. We describe here a new patient presenting a similar complete phenotype of premature ovarian failure, with high plasma FSH levels associated with very low estrogen and inhibin B levels. No biological response to high doses of recombinant FSH was detected. A novel homozygous Pro(519)Thr mutation was found in this patient. This mutation is located in the second extracellular loop of the FSH receptor, within a motif highly conserved in gonadotropin and TSH receptors. The mutation totally impairs adenylate cyclase stimulation in vitro. FSH binding experiments and confocal microscopy showed that this mutation alters the cell surface targeting of the mutated receptor, which remains trapped intracellularly. Histological studies of the ovaries of the patient showed an increase in the density of small follicles compared with age-matched normal women. A complete block in follicular maturation after the primary stage was also observed. Immunocytochemical studies allowed detection of the expression of c-Kit and proliferation cellular nuclear antigen, whereas no apoptosis was shown by the 3'-end-labeling method. This observation supports the concept that in humans FSH seems mandatory for the initiation of follicular growth only after the primary stage. In our patient complete FSH resistance yields infertility, which is remarkably associated with the persistence of a high number of small follicles.
 ...
PMID:Delayed puberty and primary amenorrhea associated with a novel mutation of the human follicle-stimulating hormone receptor: clinical, histological, and molecular studies. 1291 23

We present ovulation that occurred after the administration of traditional Chinese herbal medicine for 3 months in a woman with premature ovarian failure (POF) and secondary amenorrhea for 8 years. Traditional Chinese medicine concentrated herbal extracts of cooked rehmannia, Chinese yam, wolfberry fruit, dogwood fruit, cyathula root, dodder seed, antler glue, tortoise-plastron glue, epimedium and morinda root were prescribed, which were a modification of the herbal formula Zuo-gui-wan. When the patient discontinued the Chinese herbal medicine treatment and tried therapy with clomiphene citrate, neither ovulation nor conception occurred. Eight months after beginning clomiphene citrate therapy, the concentrations of follicle stimulating hormone and luteinizing hormone were still in the postmenopausal range. The modified formula of Zuo-gui-wan was prescribed again and the patient conceived 1 month after taking Zuo-gui-wan. Thus, we suggested that Chinese herbal medicine restored ovarian function effectively and promptly, and offers another option for treating infertility in patients with POF.
 ...
PMID:Pregnancy in premature ovarian failure after therapy using Chinese herbal medicine. 1295 93


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>