ABSTRACT
Background: Recurrent Spontaneous Abortion [RSA] is caused by multiple genetic and non-genetic factors. Around 50% of the RSA cases have no known etiology and are considered as Unexplained RSA [URSA]. Estrogens, via binding to their receptors, play an important role in female reproduction. This study aimed to investigate whether single nucleotide polymorphisms [SNPs; +1082G/A, +1730G/A and rs1256030C/T] in the estrogen receptor beta [ESR2] gene are associated with susceptibility to URSA in a population of Iranian women
Methods: In this case-control study, the study groups consisted of 240 subjects with a history of URSA and 102 fertile women as controls. Serum levels of follicle stimulating hormone [FSH], luteinizing hormone [LH], and estradiol [E2] were measured on day 2-3 of menstrual cycle. Two functional SNPs, +1082G/A [a silent mutation in exon 5] and +1730G/A [3' untranslated region of the exon 8], and one intron, rs1256030C/T, in the ESR2 gene were genotyped, using polymerase chain reaction- restriction fragment length polymorphism [PCR-RFLP] analysis
Results: Serum levels of LH were significantly increased in URSA women. No significant differences in distribution of +1082G/A, +1730G/A and rs1256030C/T between URSA and control groups were observed
Conclusion: Our findings suggest that the studied SNPs on ESR2 gene may not be associated with URSA
ABSTRACT
Emergence of drug resistance has brought major problems in chemotherapy. Using nutrients in combination with chemotherapy could be beneficial for improvement of sensitivity of tumors to drug resistance. Soybean-derived isoflavones have been suggested as chemopreventive agents for certain types of cancer, particularly breast cancer. In this study, the synergistic effects of soy isoflavone extract in combination with docetaxel in murine 4T1 breast tumor model were investigated. In this study, mice were divided into 4 groups [15 mice per group] of control, the dietary Soy Isoflavone Extract [SIE, 100 mg/kg diet], the Docetaxel [DOCE, 10 mg/kg] injection and the combination of dietary soy isoflavone extract and intravenous docetaxel injection [DOCE+SIE]. After 3 injections of docetaxel [once a week], 7 mice were sacrificed to analyze MKI67 gene and protein expressions and the rest were monitored for diet consumption, tumor growth and survival rates. In DOCE+SIE group, diet consumption was significantly higher than DOCE group. While lifespan showed a trend towards improvement in DOCE+SIE group, no significant difference was observed among the 4 studied groups. Tumor volume was not significantly affected in treated groups. A lower but not significant MKI67 protein expression was detected in western blot in DOCE+SIE group. The mRNA expression was not significantly different among groups. The results suggest that the combination of soy isoflavone as an adjunct to docetaxel chemotherapy can be effective in improving diet consumption in breast cancer
Subject(s)
Animals, Laboratory , Glycine max , Isoflavones , Plant Extracts , Taxoids , Mice , Breast NeoplasmsABSTRACT
Recurrent pregnancy loss [RPL] is a multifactorial disorder. Environmental factors and genetics can affect pregnancy outcomes. Conflicting data suggest an association between estrogen receptor alpha [ESR1] gene polymorphisms and RPL. In this study, such association was investigated in Iranian women with RPL. In this case control study, blood samples were collected from 244 women with a history of three or more consecutive pregnancy losses and 104 healthy women with at least two live births. Using polymerase chain reaction- restriction fragment length polymorphism [PCR-RFLP], we studied -397C/T and -351A/G polymorphisms on ESR1 gene in case and control subjects. The genotypic frequencies of -397C/T and -351A/G polymorphisms on ESR1were not significantly different between RPL and control groups [p=0.20 and p=0.09, respectively]. A significantly negative correlation was observed between -397C/T and -351A/G [r=-0.852, p<0.001] in RPL women and complete linkage disequilibrium between the investigated polymorphisms was found [D': 0.959; r-square= 0.758, p<0.001]. This investigation suggests that the analyzed polymorphisms on ESR1gene are not associated with an increased risk of RPL in the studied population
ABSTRACT
Recurrent abortion [RA] may be a consequence of aberrant expression of immunological factors during pregnancy. Although the relative importance of immunological factors in human reproduction remains controversial, substantial evidence suggests that autoantibodies contribute to reproductive failure. Production of such antibodies is under the control of cytokines; and leptin, besides its role in reproductive success, has a profound effect on directing the cytokine profile toward Th[1] [cellular] pattern. Therefore, the present study was performed to assess serum leptin levels in women with immunological recurrent abortion. In this prospective study, 250 women who attended Avicenna Infertility Clinic with RA were screened for known causes of abortion from July to December 2008 in Tehran, Iran. Eighty-one patients with normal karyotypes and hormonal profile with normal ovaries and uterus and no signs of infection were categorized as patients with immunological [IRA, n = 39] or unexplained [URA, n = 42] recurrent abortion based on presence or absence of autoantibodies. After blood sampling, levels of anti-nuclear antibody [ANA], anti-double stranded DNA antibody [anti-dsDNA], lupus anti-coagulant antibody [LACAb], anti-phospholipid antibody [APA], anti-cardiolipin antibody [ACA], anti-thyroglobulin antibody [TgAb], anti-thyroperoxidase antibody [TPOAb] and anti-thrombin III antibody [ATIIIAb] were measured by enzyme-linked immunosorbent assay [ELISA] or chemiluminescent enzyme immunoassay [CLEIA]. In IRA group, 9 [23.1%], 24 [61.5%], 25[64.1%] and 1 [2.6%] women were above the normal cut-off point for ANA, TgAbs, TPOAbs and AT-III Abs, respectively. IRA patients had normal values of LACAbs, APA and ACA. With normal level of fasting blood sugar [FBS], IRA and URA groups had similar serum leptin levels [23.7 +/- 13.2 ng/ml vs. 22.7 +/- 12.5 ng/ml, respectively]. Serum leptin concentrations showed a positive correlation with weight and BMI in both groups. This study suggests that serum leptin levels are higher in IRA and URA patients than normal women. The findings of this study suggest the need for a more comprehensive study and comparison of leptin levels in IRA and URA patients to women with no history of miscarriages