Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

High-dose chemotherapy and radiotherapy has increased long-term survival of young patients with cancer. Sometimes however, the price paid is ovarian failure and sterility. It is highly important to detect who are the patients at risk in order to verify when fertility preservation is indicated. With conventional chemotherapy, there is significant differences in ovarian failure rate according to patients age, disease for which patients are treated for, and the drugs used. Bone marrow transplantation in cancer patients almost invariably induced ovarian failure, irrespective of patient age, treatment protocol or administration of hormonal treatment. Moreover, normal reproductive parameters post-chemotherapy does not necessarily imply that the ovaries escaped damage; ovarian injury is not an all or none phenomenon--partial loss of primordial follicle reserve can result in premature menopause as a delayed reaction to treatment. This should be taken into account while consulting former cancer patients about future planed pregnancies. The direct mechanisms of chemotherapy induced ovarian failure are poorly understood. An in vitro study has demonstrated that in the human ovary chemotherapy acts primarily on primordial follicles through induction of apoptotic changes in pregranulosa cells which lead to follicle loss. Protecting fertility potential in females exposed to chemotherapy with IVF and embryo cryopreservation or cryopreservation of ovarian tissue is practiced. Ovarian tissue cryopreservation: A recent study has demonstrated that laparoscopic ovarian biopsy performed with the round biopter is a safe and efficient method for collecting ovarian tissue for cryopreservation in cancer patients. In order to avoid possible hazards of transferring malignant cells, genetic and immunohistochemical markers for detection of minimal residual cancer cells in ovarian tissue are currently used. However, the reproductive potential of this method is still questionable. IVF: IVF and embryocryopreservation is currently used in infertile patients, however, several obstacles prevent it's wide implementation in cancer patients such as the need for male partner and the time needed for ovarian stimulation. A highly important issue is the possible risk of performing IVF and embryo cryopreservation to preserve fertility in females already exposed to chemotherapy. An animal study has raised serious concerns regarding the consequences of chemotherapy on future pregnancies. High abortion and malformation rates related to the different stages of oocyte maturation at the time of exposure to chemotherapy were demonstrated. These results should be taken into account when considering the use of IVF and embryo cryopreservation following chemotherapy treatment in cancer patients.
Mol Cell Endocrinol 2000 Nov 27
PMID:Reproduction post-chemotherapy in young cancer patients. 1115 44

This study reports on the safety and efficiency of the cryopreservation of human embryos obtained after intracytoplasmic sperm injection. For this, we evaluated the morphological survival, the capacity of the surviving embryo to develop further in vitro and in vivo. After freezing-thawing embryos obtained after ICSI, 40% of the embryos do not survive the cryopreservation procedure. After selective transfer of further cleaving frozen-thawed embryos, pregnancy loss was 31% (subclinical pregnancy rate of 13% and miscarriage rate of 18%). As a result the livebirth rate per transferred embryos and per thawed embryo was 7 and 3% respectively. Obstetric outcome as well as further follow-up of the children born indicate that cryopreservation of ICSI embryos is a safe procedure, long term follow-up of the children born however is still warranted.
Mol Cell Endocrinol 2000 Nov 27
PMID:Embryo freezing after intracytoplasmic sperm injection. 1115 54

Spontaneous abortion of normal karyotype embryos in mice and in humans is associated with an increase in uterine T helper (Th) 1 type proinflammatory cytokines, tumour necrosis factor (TNF)-alpha, interferon-gamma and interleukin (IL)-1, and a deficiency of Th2/3 type cytokines, IL-4, IL-10, and transforming growth factor (TGF)-beta2. In mice, Th1 cytokines up-regulate a novel prothrombinase, fgl2, which via thrombin, leads to activation of polymorphonuclear leukocytes that terminate the pregnancy. Here we show that Th1 cytokines up-regulate fgl2 mRNA in fetal trophoblast and secondary decidua of CBA/JxDBA/2 and CBA/JxBALB/c matings, and promote fibrin deposition. This pattern is accompanied by a high rate of abortion. However, the spontaneous abortion rates in abortion-prone CBAxDBA/2 matings and in low abortion rate CBAxBALB/c matings were significantly lower than that expected from the frequency of implantations with high levels of fibrin and fgl2 mRNA(hi). As the glycoprotein OX-2 occurs in the pregnant rat uterus and can deviate cytokine responses to Th2/3, we investigated OX-2 in pregnant CBA/J mice. We found OX-2 mRNA was present at the same sites as fgl2 mRNA, but was reduced in response to Th1 cytokines. Furthermore, anti-OX-2 raised the abortion rate to predicted levels, while recombinant OX-2 dramatically reduced the abortion rate. Fgl2 prothrombinase may provide a mechanism explaining pregnancy loss, and conversely, successful pregnancy may be due in part to OX-2-dependent activation of maternal tolerance mechanisms at the feto-maternal interface.
Mol Hum Reprod 2001 Feb
PMID:Fgl2 prothrombinase expression in mouse trophoblast and decidua triggers abortion but may be countered by OX-2. 1116 Aug 45

Androgen receptors (AR) have been identified in the human endometrium, but their role in endometrial function and development towards endometrial receptivity remains poorly understood. In an effort to study the regulation and possible function in endometrial epithelium, we utilized the well-differentiated endometrial adenocarcinoma cell line, Ishikawa, as a model system. This cell line has proven to be stable, hormonally responsive, contains both estrogen and progesterone receptors, and has been shown to express endometrial proteins in a hormone responsive manner. In the present study, we demonstrate that Ishikawa cells also express AR, based on immunohistochemical staining, radioactive binding studies, RT-PCR and Northern blot analysis. The expression of AR is induced in Ishikawa cells by estrogens, similar to that reported for normal endometrium. Further, using an estrogen-responsive gene that has been characterized in this cell line, alkaline phosphatase, we show that androgens act as antiestrogens in diethylstilbestrol (DES) treated cells, inhibiting enzymatic activity in a dose-dependent manner. These data support a physiologic role for AR in the endometrium. Elevations in endometrial AR in certain clinical situations such as polycystic ovarian syndrome (PCOS) may amplify the effects of androgens on the endometrium leading to suspected defects in uterine receptivity, higher than expected infertility and high miscarriage rates observed in patients with this disorder.
J Steroid Biochem Mol Biol 2000 Nov 15
PMID:Characterization of androgen receptors in a well-differentiated endometrial adenocarcinoma cell line (Ishikawa). 1116 29

The activation of complement via the mannan-binding lectin (MBL) pathway is initiated by the MBL complex consisting of the carbohydrate binding molecule, MBL, two associated serine proteases, MASP-1 and MASP-2, and a third protein, MAp19. In the present report we used an assay of complement activation specifically reflecting the physiological activity of the MBL complex to identify biological and synthetic inhibitors. Inhibitor activity towards the MBL complex was compared to the inhibition of the classical pathway C1 complex and to a complex of MBL and recombinant MASP-2. A number of synthetic inhibitors were found to differ in their activities towards complement activation via the MBL pathway and the classical pathway. C1 inhibitor inhibited both pathways whereas alpha2-macroglobulin (alpha2M) inhibited neither. C1 inhibitor and alpha2M were found to be associated with the MBL complex. Upon incubation at 37 degrees C in physiological buffer, the associated inhibitors as well as MASP-1, MASP-2, and MAp19 dissociated from MBL, whereas only little dissociation of the complex occurred in buffer with high ionic strength (1 M NaCl). The difference in sensitivity to various inhibitors and the influence of high ionic strength on the complexes indicate that the activation and control of the MBL pathway differ from that of the classical pathway. MBL deficiency is linked to various clinical manifestations such as recurrent infections, severe diarrhoea, and recurrent miscarriage. On the other hand, impaired control of complement activation may lead to severe and often chronically disabling diseases. The results in the present report suggests the possibility of specifically inhibiting of the MBL pathway of complement activation.
Mol Immunol 2000 Oct
PMID:Control of the classical and the MBL pathway of complement activation. 1125 2

Polycystic ovarian syndrome (PCOS) involves follicular atresia, formation of multiple ovarian cysts and is frequently associated with a higher abortion rate. Follicular development, ovulation, formation of corpus luteum and its regression involve extensive tissue remodelling. Mammalian ovaries express a number of matrix metalloproteinases (MMP) and their tissue inhibitors (TIMP). We assessed the differences in production of MMP-2, MMP-9 and TIMP-1 by cultured luteinized granulosa cells from women with PCOS and normal ovulatory women after ovarian stimulation for IVF treatment. In follicular fluid from women with PCOS, levels of MMP-9 and MMP-2 were higher than the normal group, as was the basal production of these proteins by cultured cells. Basal production of TIMP-1 by cultured cells was not different between PCOS and normal groups. A time-dependent increase in the production of MMP-9 was observed in cells from both normal and PCOS women, although the increase was more pronounced in the latter. Thus the MMP-TIMP balance is shifted toward greater MMP activity in luteinized granulosa cells from women with PCOS.
Mol Hum Reprod 2001 Apr
PMID:The balance between MMP-9 and MMP-2 and their tissue inhibitor (TIMP)-1 in luteinized granulosa cells: comparison between women with PCOS and normal ovulatory women. 1127 94

The causes for recurrent spontaneous abortion (RSA) remain unknown in a large proportion of the cases. Human leukocyte antigen (HLA)-G and HLA-E are expressed on invasive trophoblast cells, and are supposed to confer to materno-fetal tolerance. A total of 14 different nucleotide sequences have been described for HLA-G, including one dysfunctional null allele (HLA-G*0105N), while five different sequences have been described for HLA-E. In this study, 78 RSA couples and 52 fertile controls were typed for HLA-G and HLA-E by direct sequencing or single strand conformational polymorphism (SSCP) respectively. The overall analysis showed no significant difference in allele frequencies for either HLA-G or HLA-E between the two groups. However, HLA-G allele frequencies in women who had suffered from five or more RSA differed significantly from fertile controls (P: = 0.001), and from women who had undergone three or four RSA (P: = 0.027). Detailed analysis demonstrated a significant increase in the proportion of the HLA-G alleles *01013 and *0105N in the whole group of RSA women compared with fertile controls (P: = 0.007). When studying the prognostic value of HLA genotyping for pregnancy outcome (n = 41), 31 patients (76%) gave birth to a living child without performing immunotherapy. Seven out of 10 (70%) couples suffering from a further RSA carried the HLA-G*01013 or *0105N allele, compared with 10 out 31 (32%) couples giving birth (P: = 0.06). This study suggests that the HLA-G genotype may be a contributing factor in RSA.
Mol Hum Reprod 2001 Apr
PMID:The HLA-G genotype is potentially associated with idiopathic recurrent spontaneous abortion. 1127

The use of FISH (fluorescent in situ hybridization) in decondensed sperm nuclei has allowed, during the last decade, to indirectly study the chromosome constitution of human spermatozoa. Studies in control populations have been used to set up the basal level of aneuploidy for all human chromosomes and, based on conservative estimates, the percentage of chromosomally abnormal sperm in the general population could be considered to be at least 6.7%. In carriers of sex chromosome numerical anomalies and in severe oligozoospermic males (both frequent candidates for intracytoplasmic sperm injection), in structural chromosome carriers (enrolled in preimplantation genetic diagnosis programs) and in couples with recurrent miscarriage, sperm chromosome analyses by FISH could help to better establish a reproductive prognosis.
Mol Cell Endocrinol 2001 Oct 22
PMID:Chromosomal abnormalities in sperm. 1157 33

HLA-G is a non-classical human leukocyte antigen expressed primarily in fetal tissues at the maternal-fetal interface. This expression pattern is unique among HLA genes and suggests that HLA-G may be involved in interactions that are critical in establishing and/or maintaining pregnancy. To evaluate the role of polymorphisms at this locus in maternal-fetal interactions, 113 couples with unexplained recurrent miscarriage were genotyped for seven polymorphisms that define 12 HLA-G alleles. Logistic regression analysis was used to assess whether HLA-G genotypes were associated with an increased risk for a subsequent miscarriage. The presence of an HLA-G*0104 or HLA-G*0105N allele in either partner was significantly associated with an increased risk for miscarriage, after adjustment for maternal age, number of previous miscarriages, history of a previous liveborn, and treatment with paternal mononuclear cells. The *0104 and *0105N alleles are defined by polymorphisms in the alpha-2 domain and encode protein variants that are present only in the full-length HLA-G1 protein. The significant genotype-specific risk in this population suggests that allelic variation in the alpha-2 domain of the HLA-G1 isoforms contributes to recurrent miscarriage.
Mol Hum Reprod 2001 Dec
PMID:HLA-G genotypes and pregnancy outcome in couples with unexplained recurrent miscarriage. 1171 94

Interleukin (IL)-1beta, angiotensinogen (Agt), and endothelium-derived nitric oxide synthase (eNOS) are thought to be involved in idiopathic recurrent miscarriage (IRM). We investigated the correlation between IRM and common polymorphisms in Agt, Nos3 and IL-1beta genes: one polymorphism in the promoter region of the IL-1beta gene, one in exon 2 of the Agt gene, and one in exon 7 of the Nos3 gene. A total of 130 women with a history of IRM and 67 healthy control women were included in the study. Genotyping for the C/T transition at position -511 in the promoter region of IL1B, for the single base M235T polymorphism of Agt, and for the missense Glu298Asp variant of Nos3 was performed using PCR, an allele-specific oligonucleotide hybridization assay, and pyrosequencing, respectively. Allele and genotype frequencies of all polymorphisms were similar among women with IRM and controls. Between women with primary and secondary recurrent miscarriages, no statistically significant differences between allele and genotype frequencies were observed. Despite promising experimental data, our data fall short of showing any significant association between a variant of the promoter region of IL1B, the M235T polymorphism of Agt, and the Glu298Asp missense variant of Nos3 and the occurrence of IRM.
Mol Hum Reprod 2002 Jan
PMID:Polymorphisms of the angiotensinogen gene, the endothelial nitric oxide synthase gene, and the interleukin-1beta gene promoter in women with idiopathic recurrent miscarriage. 1175 75


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