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Tehrani F.R.,Reproductive Endocrinology Research Center | Noroozzadeh M.,Reproductive Endocrinology Research Center | Zahediasl S.,Research Institute for Endocrine science | Piryaei A.,Shahid Beheshti University of Medical Sciences | Azizi F.,Shahid Beheshti University of Medical Sciences
Experimental Physiology | Year: 2014

New Findings: What is the central question of this study? Would it be possible to produce a rat model of polycystic ovary syndrome (PCOS), in which the fetuses are exposed to testosterone for a short time and exhibit both endocrine and ovarian disturbances similar to PCOS, while maintaining normal reproductive system morphology in adulthood? What is the main finding and its importance? Prenatal exposure to a single dose of testosterone during the critical period of fetal development facilitates the production of a functional rat model of PCOS with minimal morphological disorders in adulthood. Production of a functional rat model that resembles many features of PCOS may contribute to a better understanding of this syndrome. Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women, with a prevalence of 8-12% during the reproductive years. In the present study, using prenatal exposure to a single dose of testosterone during the critical period of fetal development, we aimed to introduce an enhanced rat model that would exhibit both endocrine and ovarian disturbances similar to PCOS, while maintaining normal reproductive system morphology in adulthood. Ten pregnant rats were injected s.c. with 5 mg free testosterone on gestational day 20, while control rats received only solvent. The development and function of the reproductive system in female offspring were examined in adulthood. Prenatally androgenized offspring had irregular oestrous cycles compared with control animals, and their anogenital and anovaginal distances were increased compared with control rats (P < 0.001). No significant differences were observed in the lengths of the vagina and clitoris or the number of nipples between the two groups. Levels of testosterone and luteinizing hormone and the luteinizing hormone/follicle-stimulating hormone ratio were increased in prenatally androgenized offspring compared with control animals (P < 0.05). The numbers of preantral and antral follicles in the ovaries of prenatally androgenized offspring were also increased compared with control rats (P = 0.07 and P < 0.01, respectively). The number of corpora lutea was decreased in prenatally androgenized offspring compared with control rats. Cystic follicles were observed in the ovaries of prenatally androgenized offspring. Prenatal exposure to a single dose of testosterone during the critical period of fetal development could facilitate the development a functional rat model of PCOS in adulthood, with minimal morphological disorders in the reproductive system. © 2014 The Physiological Society. Source


Ramezani Tehrani F.,Research Institute for Endocrine science | Dolleman M.,University Utrecht | Van Disseldorp J.,University Utrecht | Broer S.L.,University Utrecht | And 6 more authors.
Climacteric | Year: 2014

Objective This study aimed to cross-validate two comparable Weibull models of prediction of age at natural menopause from two cohorts, the Scheffer, van Rooij, de Vet (SRV) cohort and the Tehran Lipid and Glucose Study (TLGS) cohort. It summarizes advantages and disadvantages of the models and underlines the need for achieving correct time dependency in dynamic variables like anti-Müllerian hormone. Methods Models were fitted in the original datasets and then applied to the cross-validation datasets. The discriminatory capacity of each model was assessed by calculating C-statistics for the models in their own data and in the cross-validation data. Calibration of the models on the cross-validation data was assessed by measuring the slope, intercept and Weibull shape parameter. Results The C-statistic for the SRV model on the SRV data was 0.7 (95% confidence interval (CI) 0.7-0.8) and on the TLGS data it was 0.8 (95% CI 0.8-0.9). For the TLGS model on the TLGS data, it was 0.9 (95% CI 0.8-0.9) and on the SRV data it was 0.7 (95% CI 0.6-0.8). After calibration of the SRV model on the TLGS data, the slope was 1, the intercept -0.3 and the shape parameter 1.1. The TLGS model on the SRV data had a slope of 0.3, an intercept of 12.7 and a shape parameter of 0.6. Conclusions Both models discriminate well between women that enter menopause early or late during follow-up. While the SRV model showed good agreement between the predicted risk of entering menopause and the observed proportion of women who entered menopause during follow-up (calibration) in the cross-validation dataset, the TLGS model showed poor calibration. © 2014 International Menopause Society. Source


Pooyan H.,Islamic Azad University at Tehran | Ahmad E.,Research Institute for Endocrine science | Azadeh R.,Shahid Beheshti University of Medical Sciences
Asian Pacific Journal of Cancer Prevention | Year: 2015

Background: Glioblastoma is a highly aggressive and malignant brain tumor. Risk factors are largely unknown however, although several biomarkers have been identified which may support development, angiogenesis and invasion of tumor cells. One of these biomarkers is PAI-1. 4G/5G and A-844G are two common polymorphisms in the gene promotor of PAI 1 that may be related to high transcription and expression of this gene. Studies have shown that the prevalence of the 4G and 844G allele is significantly higher in patients with some cancers and genetic disorders. Materials and Methods: We here assessed the association of 4G/5G and A-844G polymorphisms with glioblastoma cancer risk in Iranians in a case-control study. All 71 patients with clinically confirmed and 140 volunteers with no history and symptoms of glioblastoma as control group were screened for 4G/5G and A-844G polymorphisms of PAI-1, using ARMS-PCR. Genotype and allele frequencies of case and control groups were analyzed using the DeFinetti program. Results: Our results showed significant associations between 4G/5G (p=0.01824) and A-844G (p = 0.02012) polymorphisms of the PAI-1 gene with glioblastoma cancer risk in our Iranian population. Conclusions: The results of this study supporting an association of the PAI-1 4G/5G (p=0.01824) and A-844G (p = 0.02012) polymorphisms with increasing glioblastoma cancer risk in Iranian patients. Source


Tehrani F.R.,Shahid Beheshti University of Medical Sciences | Tehrani F.R.,Research Institute for Endocrine science | Solaymani-Dodaran M.,Tehran University of Medical Sciences | Solaymani-Dodaran M.,University of Nottingham | And 3 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2013

Context: Anti-Mullerian hormone (AMH) has already been used for prediction of age at menopause with promising results. Objective: We aimed to improve our previous prediction of age at menopause in a population-based cohort by including all eligible subjects and additional follow-up time. Design and Setting: All reproductive-aged women who met our eligibility criteria were selected from the Tehran Lipid and Glucose Study. The serum concentration of AMH was measured at the time of recruitment, and participant's date of menopause was recorded over a 10-year follow-up. Subjects: Atotal of 1015 women, aged 20 to 50 years, with regular and predictable menstrual cycles at the initiation of the study were recruited. Main Outcome Measure: The actual ages at menopause were compared with the predicted ones obtained from accelerated failure time model. Results:Weobserved 277 occurrences of menopause. Median menopausal age was 50 years (range 30.1-58.2 years). The median (SD) of differences between the actual menopausal age and those predicted by our model was 0.5 (2.5) years. Model adequacy (measured by C-statistics) for correct prediction of age at menopause was 92%. The estimated ages at menopause and their 95% confidence intervals for a range of values of AMH and age were calculated and summarized in a table. Conclusions: Using a model built on age and AMH, we can predict age at menopause many years earlier. This could provide opportunities for interventions in those who are at risk of early or late menopause. Copyright © 2013 by The Endocrine Society. Source


Mansour-Ghanaei F.,Guilan University | Joukar F.,Guilan University | Khalili D.,Research Institute for Endocrine science | Valeshabad A.K.,Guilan University
Journal of Vaccines and Vaccination | Year: 2012

Background: Specific vaccine therapies have been proposed recently as possible alternative treatment modalities to interferon and antiviral drugs to enhance the immune response in HBV chronic carriers through induction of T cell activity which can lead to control viremia. To assess the efficacy of long term intradermal (ID) hepatitis B virus (HBV) vaccination with double standard dose as an active immunotherapy in elimination of HBV infection in chronic hepatitis B carriers. Materials and Methods: This double-blinded randomized clinical trial was conducted on all HBsAg positive patients. Among them 80 immunotolerant patients were recruited and randomly allocated to alternate study groups (vaccination or placebo) consecutively. Eligible healthy carriers in group 1 were assigned to vaccinate with six ID injections of the Heberbiovac HB vaccine at 30-day intervals and with double standard doses (2cc) in two forearms. Controls received normal saline with the same setting as a placebo. The mean ALT levels, detectable HBV DNA and seroconversion to anti-hepatitis B e antigen (anti-HBe) and anti hepatitis B surface antigen (anti-HBsAb) compared between groups at the beginning and the 6th and 12th months. Results: No significant difference was found in the mean ALT values, the clearance of HBV DNA, seroconversion from HBeAg to HBeAb and developing of HBsAb between vaccinated and control group at the end of the 6th and 12th months (P>0.05). Conclusion: Intradermal administration, even with double standard dose, is not an efficient treatment in the elimination of virus in chronic carriers of HBV.© 2012 Mansour-Ghanaei F, et al. Source

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