Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C1140680 (ovarian cancer)
 28,141 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A survey of 108 heterozygote women for the classic galactosemia gene, GALT, did not reveal that the carrier state was associated with premature ovarian failure or ovarian cancer. This survey did not support previous epidemiologic studies suggesting an increased risk for ovarian dysfunction in women with deficiency of the GALT enzyme.
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PMID:Results of a survey of carrier women for the galactosemia gene. 840 35

Many US women remain unaware of the noncontraceptive health benefits associated with oral contraceptive (OC) use. An extensive body of research has established that OCs protect women against dysmenorrhea and menorrhagia, menstrual cycle irregularities, iron deficiency anemia, ectopic pregnancy, pelvic inflammatory disease, ovarian cysts, benign breast disease, and endometrial and ovarian cancer. More recent studies have suggested that OCs can be used for the treatment of acne vulgaris and the prevention of osteopenia in hypoestrogenic women. In addition to these classic and emerging noncontraceptive health benefits, many clinicians prescribe OCs for the treatment of common gynecologic conditions such as dysfunctional uterine bleeding, polycystic ovarian syndrome, premature ovarian failure, pelvic pain, mittelschmertz, endometriosis, and control of bleeding in women with blood dyscrasias. If OC acceptors are educated about these benefits, contraceptive compliance and continuation are likely to improve.
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PMID:Oral contraceptive health benefits: perception versus reality. 1034 94

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.
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PMID:[Oocyte donation to be legalized in Sweden. Excellent results reported from other countries]. 1219 31

Chronically elevated luteinizing hormone (LH) induces significant pathology in the LHbetaCTP transgenic mouse model, which uses the bovine gonadotropin alpha (alpha)-subunit promoter to direct transgene expression specifically to gonadotropes in the anterior pituitary. Previously, it was shown that female LHbetaCTP mice are infertile due to anovulation, develop granulosa cell tumors, and undergo precocious puberty from elevated LH and steroid hormones that fail to completely repress the alpha-subunit promoter. This chapter will discuss recent studies that further elucidate the impact of chronically elevated LH on diverse physiological systems. Granulosa cell tumors induced by elevated LH are strain dependent and prevented when transgenics are treated with human chorionic gonadotropin (hCG) surges. A granulosa cell tumor-associated transcriptome is generated, revealing several possible gene candidates for ovarian granulosa cell tumorigenesis. Primordial follicles in LHbetaCTP transgenics become depleted and oocytes exhibit increased rates of meiotic segregation defects, although meiotic competency is acquired normally. Anovulation can be rescued in transgenics by superovulation, though pregnancy fails at midgestation due to maternal factors. Uterine receptivity defects prevent implantation of normal embryos following induction of pseuodpregnancy. Transgenics develop Cushing-like adrenocortical hyperfunction with increased corticosterone production following induction of adrenal LH receptor expression. Elevated LH acts as a tumor promoter in the gonads and the adrenal gland, when expressed in conjunction with the inhibin-alpha SV40 transgene. Finally, chronic elevated LH promotes mammary tumorigenesis. The understanding of multiple clinical pathologies--including ovarian cancer, perimenopausal reproductive aging, premature ovarian failure, polycystic ovarian syndrome, Cushing's syndrome, and breast cancer--may be enhanced through further study of this useful transgenic mouse model.
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PMID:Consequences of elevated luteinizing hormone on diverse physiological systems: use of the LHbetaCTP transgenic mouse as a model of ovarian hyperstimulation-induced pathophysiology. 1279 27

Animal models with premature ovarian failure resulting from the loss or depletion of germ cells consistently develop ovarian surface epithelial cell hyperplasia with invasion into the stroma and the development of ovarian tubular adenomas. In human ovaries, deep epithelial invaginations and inclusion cysts occur at increasing frequency with age and are thought to be the structures from which the majority of ovarian cancers arise. A feature that is common to these animal models and to post-menopausal women is a deficiency in the number of oocytes. The potential consequences of the loss or depletion of female germ cells, naturally or otherwise, include failure of follicle development, significant reductions in oestrogen and progesterone levels and elevation of circulating levels of gonadotropins. This review will consider the way in which these structural and hormonal changes affect ovarian cancer risk. Some lessons may be learned from gonad formation, since notable similarities exist between ovarian tumorigenesis and embryonic gonadogenesis including fragmentation of the basement membrane underlying the coelomic (surface) epithelium, the potential for the migration of epithelial cells into the gonad and the importance of the germ cells for the regulation of ovarian structure and function.
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PMID:Loss of ovarian function and the risk of ovarian cancer. 1590 2

Orphan nuclear receptors such as germ cell nuclear factor (GCNF), steroidogenic factor 1 (SF-1) and liver receptor homolog-1 (LRH-1), are emerging as important ovarian factors in regulating female reproduction. Within the ovary, GCNF (NR6A1) expression is restricted to the oocyte, while SF-1 (NR5A1) is expressed only in the somatic cells, such as granulosa, thecal and luteal cells, and interstitial cells. LRH-1 (NR5A2), an orphan receptor closely related to SF-1, is expressed only in the granulosa cells of the follicles and luteal cells within the ovary. Recent studies using conditional knockout strategies to bypass the embryonic lethality of GCNF and SF-1 null mice have uncovered important roles of GCNF and SF-1 in the oocyte and granulosa cells, respectively. In this review, we will summarize the major findings of GCNF and SF-1 in the ovary from the studies of conditional GCNF and SF-1 knockout mice. The potential role of LRH-1 in the ovary is also briefly discussed. Understanding the ovarian functions of these orphan nuclear receptors may lead to the development of new agents for regulation of female fertility and new medicines for the treatment of female idiopathic infertility, premature ovarian failure, polycystic ovarian syndrome and ovarian cancer.
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PMID:Orphan nuclear receptor function in the ovary. 1748 8

3-Methylcholanthrene (3MC) is a potent ovotoxicant capable of causing premature ovarian failure through primordial follicle depletion. Despite 3MCs ovotoxicity having been established for 30 years, relatively little information exists on the mechanisms. In this study, we examined the effects of 3MC exposure on the immature ovarian follicle population. Microarray analysis revealed a complex mechanism of 3MC-induced ovotoxicity involving a number of cellular processes associated with xenobiotic metabolism, ovarian cancer, cell cycle progression, and cell death. 3MC exposure was also found to induce developing follicle atresia and aberrant primordial follicle activation via the stimulation of PI3K/Akt and mammalian target of rapamycin (mTOR) signaling pathways. Inhibition of PI3K/Akt signaling resulted in the severe depletion of the primordial follicle pool, with further analysis identifying increased Akt1-stimulated Bad phosphoinhibition in 3MC-treated primordial follicles. Our results suggest that the primordial follicle pool enters a "prosurvival" state upon 3MC exposure and that its depletion is due to a vicious cycle of primordial follicle activation in an attempt to replace developing follicles undergoing follicular atresia.
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PMID:Staying alive: PI3K pathway promotes primordial follicle activation and survival in response to 3MC-induced ovotoxicity. 2250 44

Unlike men, who have continuous spermatogenesis throughout most of their lifetime, women are born with a fixed supply of follicles, and this number progressively declines with age until the menopause. Beside age, the speed of follicle depletion can be regulated by genetic, hormonal and environmental influences. In the course of their lives, women are exposed to multiple chemicals and radiation sources that can increase the chance of developing permanent infertility and premature ovarian failure (POF). A wealth of experimental data indicate that iatrogenic (chemotherapy, radiotherapy) and xenobiotic agents (e.g., chemicals, pharmaceuticals) are potent ovotoxicants capable of accelerating ovarian reserve depletion. In the present review we reported the negative effects exerted on mammalian ovary by some widely diffused environmental chemicals, as polycyclic aromatic hydrocarbons (PAHs) and dithiocarbamate mancozeb, and by 1-3 butadiene and 4-vinylcycloexene, two occupational chemicals known to be capable of inducing ovarian cancer and infertility. Furthermore, attention has been devoted to the consequences of chemo- and radiotherapy on the ovary, both known to affect reproductive lifespan. Our increasing understanding of metabolic alterations induced by these agents is fundamental to individuate new therapeutic strategies aimed to prevent ovarian dysfunction in fertile women.
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PMID:Ovarian toxicity: from environmental exposure to chemotherapy. 2450 97

Despite extensive research, genetic basis of premature ovarian failure (POF) and ovarian cancer still remains elusive. It is indeed paradoxical that scientists searched for mutations in FSH receptor (FSHR) expressed on granulosa cells, whereas more than 90% of cancers arise in ovary surface epithelium (OSE). Two distinct populations of stem cells including very small embryonic-like stem cells (VSELs) and ovarian stem cells (OSCs) exist in OSE, are responsible for neo-oogenesis and primordial follicle assembly in adult life, and are modulated by FSH via its alternatively spliced receptor variant FSHR3 (growth factor type 1 receptor acting via calcium signaling and the ERK/MAPK pathway). Any defect in FSH-FSHR3-stem cell interaction in OSE may affect folliculogenesis and thus result in POF. Ovarian aging is associated with a compromised microenvironment that does not support stem cell differentiation into oocytes and further folliculogenesis. FSH exerts a mitogenic effect on OSE and elevated FSH levels associated with advanced age may provide a continuous trigger for stem cells to proliferate resulting in cancer, thus supporting gonadotropin theory for ovarian cancer. Present review is an attempt to put adult ovarian biology, POF, aging, and cancer in the perspective of FSH-FSHR3-stem cell network that functions in OSE. This hypothesis is further supported by the recent understanding that: i) cancer is a stem cell disease and OSE is the niche for ovarian cancer stem cells; ii) ovarian OCT4-positive stem cells are regulated by FSH; and iii) OCT4 along with LIN28 and BMP4 are highly expressed in ovarian cancers.
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PMID:FSH-FSHR3-stem cells in ovary surface epithelium: basis for adult ovarian biology, failure, aging, and cancer. 2526 15

The present review aims to ascertain whether different infertility etiologies share particular genes and/or molecular pathways with other pathologies and are associated with distinct and particular risks of later-life morbidity and mortality. In order to reach this aim, we use two different sources of information: (1) a public web server named DiseaseConnect ( http://disease-connect.org ) focused on the analysis of common genes and molecular mechanisms shared by diseases by integrating comprehensive omics and literature data; and (2) a literature search directed to find clinical comorbid relationships of infertility etiologies with only those diseases appearing after infertility is manifested. This literature search is performed because DiseaseConnect web server does not discriminate between pathologies emerging before, concomitantly or after infertility is manifested. Data show that different infertility etiologies not only share particular genes and/or molecular pathways with other pathologies but they have distinct clinical relationships with other diseases appearing after infertility is manifested. In particular, (1) testicular and high-grade prostate cancer in male infertility; (2) non-fatal stroke and endometrial cancer, and likely non-fatal coronary heart disease and ovarian cancer in polycystic ovary syndrome; (3) osteoporosis, psychosexual dysfunction, mood disorders and dementia in premature ovarian failure; (4) breast and ovarian cancer in carriers of BRCA1/2 mutations in diminished ovarian reserve; (5) clear cell and endometrioid histologic subtypes of invasive ovarian cancer, and likely low-grade serous invasive ovarian cancer, melanoma and non-Hodgkin lymphoma in endometriosis; and (6) endometrial and ovarian cancer in idiopathic infertility. The present data endorse the principle that the occurrence of a disease (in our case infertility) is non-random in the population and suggest that different infertility etiologies are genetically and clinically linked with other diseases in single meta-diseases. This finding opens new insights for clinicians and reproductive biologists to treat infertility problems using a phenomic approach instead of considering infertility as an isolated and exclusive disease of the reproductive system/hypothalamic-pituitary-gonadal axis. In agreement with a previous validation analysis of the utility of DiseaseConnect web server, the present study does not show a univocal correspondence between common gene expression and clinical comorbid relationship. Further work is needed to untangle the potential genetic, epigenetic and phenotypic relationships that may be present among different infertility etiologies, morbid conditions and physical/cognitive traits.
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PMID:Infertility etiologies are genetically and clinically linked with other diseases in single meta-diseases. 2658 2


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