Effects of Soy Isoflavones, Resistant Starch and Antibiotics on Polycystic Ovary Syndrome (PCOS)-Like Features in Letrozole-Treated Rats.
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SUBMITTER: Liyanage GSG
PROVIDER: S-EPMC8621859 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ContextSoy is the main source of phytoestrogens, which has long been used as traditional food. One major subtype of phytoestrogens includes isoflavones and they are scientifically validated for their beneficial actions on many hormone-dependent conditions.ObjectiveThe present study examines the effect of soy isoflavones on letrozole-induced polycystic ovary syndrome (PCOS) rat model.Materials and methodsPCOS was induced in Sprague-Dawley rats with of 1?mg/kg letrozole, p.o. once daily for 21 consecutive days. Soy isoflavones (50 and 100?mg/kg) was administered for 14 days after PCOS induction. Physical parameters (body weight, oestrous cycle determination, ovary and uterus weight) metabolic parameters (oral glucose tolerance test, total cholesterol), steroidal hormone profile (testosterone and 17?-oestradiol), steroidogenic enzymes (3?-hydroxy steroid dehydrogenase (HSD) and 17?-HSD), oxidative stress and histopathology of ovary were studied.ResultsSoy isoflavones (100?mg/kg) treatment significantly altered the letrozole-induced PCOS symptoms as observed by decreased body weight gain (p?<?0.05), percentage diestrous phase (p?<?0.001), testosterone (p?<?0.001), 3?-HSD (p?<?0.01) and 17?-HSD (p?<?0.001) enzyme activity and oxidative stress. Histological results reveal that soy isoflavones treatment in PCOS rats resulted in well-developed antral follicles and normal granulosa cell layer in rat ovary.DiscussionTreatment with soy isoflavones exerts beneficial effects in PCOS rats (with decreased aromatase activity) which might be due to their ability to decrease testosterone concentration in the peripheral blood.ConclusionAnalysis of physical, biochemical and histological evidences shows that soy isoflavones may be beneficial in PCOS.
| S-EPMC6130471 | biostudies-literature
Project description:<p><b>PCOS</b> is a complex genetic disease reflecting the interplay of susceptibility genes and environmental factors. The cardinal reproductive feature of the syndrome, hyperandrogenemia, appears to play a direct role in the pathogenesis of the associated metabolic abnormalities. Male as well as female first-degree relatives have reproductive and metabolic phenotypes including increased prevalence rates of type 2 diabetes (T2D), metabolic syndrome (MBS) and other risk factors for cardiovascular disease (CVD). Northwestern University (NU) investigators lead a team that has extensive experience in phenotyping PCOS and in the genetic analysis of complex diseases including genome-wide association study (GWAS). Together with an expert group of collaborators from the Hershey Medical Center, and The University of Chicago, we have conducted a GWAS to identify PCOS susceptibility alleles using a large cohort of extensively and consistently phenotyped PCOS cases. Population controls for this study come from the NUgene project described below.</p> <p><b>NUgene project</b>: In 2002, Northwestern committed to the development of a DNA repository to serve as a platform for the identification and validation of genotype-phenotype associations that will impact healthcare. The NUgene Project is a repository with longitudinal medical information from participating patients at affiliated hospitals and outpatient clinics from the Northwestern University Medical Center. Participants' DNA samples are coupled with data from a questionnaire (2 versions were used, 1 before and 1 after February 2006, both are included) and continuously updated data from our Electronic Medical Record (EMR) representing actual clinical care events. Northwestern has a state-of-the art, comprehensive inpatient and outpatient EMR system of over 2 million patients. NUgene has broad access to participant data for all outpatient visits as well as inpatient data via a consolidated data warehouse. NUgene participants consent to distribution and use of their coded DNA samples and data for a broad range of genetic research by third-party investigators.</p>
| phs000368.v1.p1 | EGA
Project description:Polycystic ovary syndrome (PCOS) is a common infertility disorder affecting a significant proportion of the global population. It is the main cause of anovulatory infertility in women and is the most common endocrinopathy affecting reproductive-aged women, with a prevalence of 8-13% depending on the criteria used and population studied. The disease is multifactorial and complex and, therefore, often difficult to diagnose due to overlapping symptoms. Multiple etiological factors have been implicated in PCOS. Due to the complex pathophysiology involving multiple pathways and proteins, single genetic diagnostic tests cannot be determined. Progress has been achieved in the management and diagnosis of PCOS; however, not much is known about the molecular players and signaling pathways underlying it. Conclusively PCOS is a polygenic and multifactorial syndromic disorder. Many genes have been associated with PCOS, which affect fertility either directly or indirectly. However, studies conducted on PCOS patients from multiple families failed to find a fully penetrant variant(s). The present study was designed to review the current genetic understanding of the disease. In the present review, we have discussed the clinical spectrum, the genetics, and the variants identified as being associated with PCOS. The mechanisms by which variants in the genes confer risk to PCOS and the nature of the physical and genetic interaction between the genetic elements underlying PCOS remain to be determined. Elucidation of genetic players and cellular pathways underlying PCOS will certainly increase our understanding of the pathophysiology of this syndrome. The study also discusses the current status of the treatment modalities for PCOS, which is important to find new ways of treatment.
| S-EPMC6935309 | biostudies-literature
Project description: Not available
| S-EPMC6494577 | biostudies-literature
Project description:BackgroundClomiphene is the current first-line infertility treatment in women with the polycystic ovary syndrome, but aromatase inhibitors, including letrozole, might result in better pregnancy outcomes.MethodsIn this double-blind, multicenter trial, we randomly assigned 750 women, in a 1:1 ratio, to receive letrozole or clomiphene for up to five treatment cycles, with visits to determine ovulation and pregnancy, followed by tracking of pregnancies. The polycystic ovary syndrome was defined according to modified Rotterdam criteria (anovulation with either hyperandrogenism or polycystic ovaries). Participants were 18 to 40 years of age, had at least one patent fallopian tube and a normal uterine cavity, and had a male partner with a sperm concentration of at least 14 million per milliliter; the women and their partners agreed to have regular intercourse with the intent of conception during the study. The primary outcome was live birth during the treatment period.ResultsWomen who received letrozole had more cumulative live births than those who received clomiphene (103 of 374 [27.5%] vs. 72 of 376 [19.1%], P=0.007; rate ratio for live birth, 1.44; 95% confidence interval, 1.10 to 1.87) without significant differences in overall congenital anomalies, though there were four major congenital anomalies in the letrozole group versus one in the clomiphene group (P=0.65). The cumulative ovulation rate was higher with letrozole than with clomiphene (834 of 1352 treatment cycles [61.7%] vs. 688 of 1425 treatment cycles [48.3%], P<0.001). There were no significant between-group differences in pregnancy loss (49 of 154 pregnancies in the letrozole group [31.8%] and 30 of 103 pregnancies in the clomiphene group [29.1%]) or twin pregnancy (3.4% and 7.4%, respectively). Clomiphene was associated with a higher incidence of hot flushes, and letrozole was associated with higher incidences of fatigue and dizziness. Rates of other adverse events were similar in the two treatment groups.ConclusionsAs compared with clomiphene, letrozole was associated with higher live-birth and ovulation rates among infertile women with the polycystic ovary syndrome. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; ClinicalTrials.gov number, NCT00719186.).
| S-EPMC4175743 | biostudies-literature
Project description:Polycystic ovary syndrome (PCOS) is a heterogeneous condition which is related to an endocrine reproductive disorder of females. It affects females of 18-44 age. The persistent hormonal disbalance leads to the complexities such as numerous cysts, an irregular menstrual cycle that ultimately leads to infertility among females. Many candidate genes have been identified to be one of the causes of PCOS. Different studies have been carried out to find the genetic correlation of PCOS. It is essential to carry out such studies that identify the clear cause of PCOS and its genetic association and hormonal disbalance. This review has highlighted different genes and their correlation with PCOS that leads to hormonal disbalance. Yet not in-depth but an attempt to study the genetic predisposition of PCOS.
| S-EPMC6687436 | biostudies-literature
Project description:Polycystic ovary syndrome (PCOS) is the commonest endocrine abnormality in women of reproductive age typically presenting with chronic oligo- or anovulation, clinical, or biochemical hyperandrogenism and polycystic ovarian morphology (PCOM). Restoring mono-ovulation is the ultimate goal of ovulation induction and most women do respond to ovulation inducing agents causing their Follicle-stimulating hormone (FSH) levels to rise. Familial clustering and the results from twin studies strongly support an underlying genetic basis for PCOS. Recent Genome wide association studies (GWAS) have identified several genetic variants being genome wide significantly associated with PCOS. Amongst those are variants in or near the Luteinizing hormone (LH) and FSH receptor genes as well as a variant in the FSH-β gene. The aim of this review is to summarize the available evidence as to whether single nucleotide polymorphisms are able to modify the PCOS phenotype or whether they constitute a risk factor for the syndrome. Data on the role of FSHR polymorphisms in PCOS are conflicting. It seems that in large Chinese studies FSHR polymorphisms are not associated with either PCOS risk or with PCOS treatment outcome. However, in large scale studies in Caucasians these polymorphisms seem to influence the risk of having PCOS. Moreover, these studies also showed that some polymorphisms might affect some clinical features of PCOS as well as treatment outcome. Although most research has focussed on the role of FSHR polymorphisms there seems to be also some evidence showing that single nucleotide polymorphisms (SNPs) in the LHCG-Receptor as well as those in FSH-β gene might also alter the phenotype of PCOS. In conclusion most studies confirm that FSHR polymorphisms do alter the phenotype of PCOS in that they either alter the response to exogenous FSH or hat they increase the risk of having PCOS.
| S-EPMC6379247 | biostudies-literature
Project description:Polycystic ovary syndrome (PCOS) was hypothesized to result from functional ovarian hyperandrogenism (FOH) due to dysregulation of androgen secretion in 1989-1995. Subsequent studies have supported and amplified this hypothesis. When defined as otherwise unexplained hyperandrogenic oligoanovulation, two-thirds of PCOS cases have functionally typical FOH, characterized by 17-hydroxyprogesterone hyperresponsiveness to gonadotropin stimulation. Two-thirds of the remaining PCOS have FOH detectable by testosterone elevation after suppression of adrenal androgen production. About 3% of PCOS have a related isolated functional adrenal hyperandrogenism. The remaining PCOS cases are mild and lack evidence of steroid secretory abnormalities; most of these are obese, which we postulate to account for their atypical PCOS. Approximately half of normal women with polycystic ovarian morphology (PCOM) have subclinical FOH-related steroidogenic defects. Theca cells from polycystic ovaries of classic PCOS patients in long-term culture have an intrinsic steroidogenic dysregulation that can account for the steroidogenic abnormalities typical of FOH. These cells overexpress most steroidogenic enzymes, particularly cytochrome P450c17. Overexpression of a protein identified by genome-wide association screening, differentially expressed in normal and neoplastic development 1A.V2, in normal theca cells has reproduced this PCOS phenotype in vitro. A metabolic syndrome of obesity-related and/or intrinsic insulin resistance occurs in about half of PCOS patients, and the compensatory hyperinsulinism has tissue-selective effects, which include aggravation of hyperandrogenism. PCOS seems to arise as a complex trait that results from the interaction of diverse genetic and environmental factors. Heritable factors include PCOM, hyperandrogenemia, insulin resistance, and insulin secretory defects. Environmental factors include prenatal androgen exposure and poor fetal growth, whereas acquired obesity is a major postnatal factor. The variety of pathways involved and lack of a common thread attests to the multifactorial nature and heterogeneity of the syndrome. Further research into the fundamental basis of the disorder will be necessary to optimally correct androgen levels, ovulation, and metabolic homeostasis.
| S-EPMC5045492 | biostudies-literature
Project description:BackgroundPolycystic ovary syndrome (PCOS) affects 10% of reproductive-aged women, and is marked by irregular menses and high androgens. PCOS is a known risk factor for imaging-confirmed steatosis, and we now aim to evaluate whether PCOS influences histologic severity of non-alcoholic fatty liver disease (NAFLD).MethodsRetrospective study of women ages 18-45 years with biopsy-confirmed NAFLD between 2008 and 2019. Metabolic comorbidities were captured within 6 months of biopsy. Histologic features of non-alcoholic steatohepatitis (NASH) were independently evaluated by two pathologists blinded to PCOS status.ResultsAmong 102 women meeting study criteria, 36% (n = 37) had PCOS; median age was 35 years; 27% were white, 6% black, 19% Asian and 47% reported Hispanic ethnicity. Women with PCOS had higher LDL (122 vs 102 mg/dL, P = .05) and body mass index(BMI) (38 vs 33 kg/cm2 , P < .01). NASH was present in 76% of women with PCOS vs 66% without PCOS (P = .3), and a higher proportion with PCOS had severe ballooning (32% vs 13%, P = .02), presence of any fibrosis (84% vs 66%, P = .06) and advanced fibrosis (16% vs 6%, P = .10). Adjusted for age and BMI, PCOS remained associated with severe hepatocyte ballooning (OR 3.4, 95% CI 1.1-10.6, P = .03) and advanced fibrosis (OR 7.1, 95% CI 1.3-39, P = .02). Among women with advanced fibrosis, median age was 5 years younger in those with as compared to those without PCOS (40 vs 45 years, P = .02).ConclusionPolycystic ovary syndrome is independently associated with more severe NASH, including advanced fibrosis. Hepatologists should routinely inquire about PCOS in reproductive-aged women with NAFLD, and evaluate for more severe liver disease in this population.
| S-EPMC6980925 | biostudies-literature
Project description:Polycystic ovary syndrome (PCOS) is an endocrinal disorder that afflicts mainly women of childbearing age. The symptoms of PCOS are irregular menstrual cycles, weight gain, subfertility and infertility. However, because the etiology is unclear, management and treatment methods for PCOS are not well established. Recently, natural substances have been used for PCOS therapy. Ecklonia cava (E. cava) is a well-known natural substance that attenuates the effects of inflammation, allergies, and cancer. In this study, we investigated the effects of E. cava extract in rats with PCOS. When rats with letrozole-induced PCOS were exposed to the E. cava extract, the regular estrus cycle was restored, similar to that in placebo rats. Hormone levels, including the levels of testosterone, estrogen, luteinizing hormone (LH), follicle stimulating hormone (FSH), and anti-Müllerian hormone (AMH), were restored to their normal states. Histological analysis revealed that the polycystic ovary symptoms were significantly decreased in the E. cava-treated rats and were comparable to those of normal ovaries. At the transcriptional and translational levels, Ar, and Esr2 levels were markedly increased in the E. cava-treated rats with PCOS compared with the rats with letrozole-induced PCOS. These results suggest that the E. cava extract inhibits the symptoms of PCOS by restoring imbalanced hormonal levels and irregular ovarian cycles in letrozole-induced female rats.
| S-EPMC6262357 | biostudies-literature