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https://www.readbyqxmd.com/read/28442024/intracytoplasmic-oxidative-stress-reverses-epigenetic-modifications-in-polycystic-ovary-syndrome
#1
Fatemeh Eini, Marefat Ghaffari Novin, Khojasteh Joharchi, Ahmad Hosseini, Hamid Nazarian, Abbas Piryaei, Arash Bidadkosh
In polycystic ovary syndrome (PCOS), substantial genetic and environmental alterations, along with hyperandrogenism, affect the quality of oocytes and decrease ovulation rates. To determine the mechanisms underlying these alterations caused specifically by an increase in plasma androgens, the present study was performed in experimentally-induced PCOS mice. As the study model, female B6D2F1 mice were treated with dehydroepiandrosterone (DHEA, 6mg per 100g bodyweight). After 20 days, oocytes at the germinal vesicle and metaphase II stages were retrieved from isolated ovaries and subsequent analyses of oocyte quality were performed for each mouse...
April 26, 2017: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/28324041/line1-cpg-dna-hypomethylation-in-granulosa-cells-and-blood-leukocytes-is-associated-with-pcos-and-related-traits
#2
Pooja Sagvekar, Vijay Mangoli, Sadhana Desai, Anushree Patil, Srabani Mukherjee
Context: Altered global DNA methylation is indicative of epigenomic instability concerning chronic diseases. Investigating its incidence and association with polycystic ovary syndrome (PCOS) is essential to understand the etiopathogenesis of this disorder. Objectives: We assessed global DNA methylation differences in peripheral blood leukocytes (PBLs) and cumulus granulosa cells (CGCs) of controls and women with PCOS; and their association with PCOS and its traits...
April 1, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28277126/alteration-in-follistatin-gene-expression-detected-in-prenatally-androgenized-rats
#3
Marziyeh Salehi Jahromi, Fahimeh Ramezani Tehrani, Jennifer W Hill, Mahsa Noroozzadeh, Maryam Zarkesh, Asghar Ghasemi, Azita Zadeh-Vakili
Impaired ovarian follicle development, the hallmark of polycystic ovarian syndrome (PCOS), is believed to be due to the changes in expression of related genes such as follistatin (FST). Expression of FST gene and methylation level of its promoter in theca cells from adult female rats, prenatally exposed to androgen excess, during different phases of the estrus cycle was determined and compared with controls. Eight pregnant Wistar rats (experimental group) were treated by subcutaneous injection of 5 mg free testosterone on day 20 of pregnancy, while controls (n = 8) received 500 ml solvent...
February 26, 2017: Gynecological Endocrinology
https://www.readbyqxmd.com/read/28079802/promoter-methylation-of-yes-associated-protein-yap1-gene-in-polycystic-ovary-syndrome
#4
Li-Le Jiang, Juan-Ke Xie, Jin-Quan Cui, Duo Wei, Bao-Li Yin, Ya-Nan Zhang, Yuan-Hui Chen, Xiao Han, Qian Wang, Cui-Lian Zhang
BACKGROUND: DNA methylation modification has been proved to influence the phenotype of polycystic ovary syndrome (PCOS). Genome-wide association studies (GWAS) demonstrate that yes-associated protein (YAP1) genetic sites are associated with PCOS. The study aims to detect the methylation status of YAP1 promoter in ovary granulosa cells (GCs) of PCOS patients and explore novel therapeutic targets for PCOS. METHODS: Randomized controlled trial was applied and a total of 72 women were included in the study, including 36 cases of PCOS patients and 36 cases of health controls...
January 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27889100/epigenetic-regulation-of-an-adverse-metabolic-phenotype-in-polycystic-ovary-syndrome-the-impact-of-the-leukocyte-methylation-of-ppargc1a-promoter
#5
Hongcui Zhao, Yue Zhao, Yun Ren, Min Li, Tianjie Li, Rong Li, Yang Yu, Jie Qiao
OBJECTIVE: To investigate PPARGC1A promoter methylation and mitochondria DNA (mtDNA) content in the leukocytes of women with polycystic ovary syndrome (PCOS) and analyze the relationship between these indices and metabolic risk for women with PCOS. DESIGN: Cross-sectional study. SETTING: University hospital. PATIENT(S): A total of 175 women with PCOS and 127 healthy controls. INTERVENTION(S): None...
February 2017: Fertility and Sterility
https://www.readbyqxmd.com/read/27426126/translational-insight-into-polycystic-ovary-syndrome-pcos-from-female-monkeys-with-pcos-like-traits
#6
David H Abbott, Jon E Levine, Daniel A Dumesic
Genetics-based studies of women with polycystic ovary syndrome (PCOS) implicate >20 PCOS risk genes that collectively account for <10% of PCOS. Clinicians now consider that either rare alleles or non-genetic, potentially epigenetic, developmental origins may contribute key pathogenic components to >90% of PCOS cases. Animal models convincingly demonstrate excess fetal testosterone exposure in females as a reliable, epigenetic, developmental origin for PCOS-like traits. In particular, nonhuman primates (NHPs) provide the most faithful emulation of PCOS-like pathophysiology, likely because of close similarities to humans in genomic, developmental, reproductive and metabolic characteristics, as well as aging...
2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27358825/epigenetic-modification-of-long-interspersed-elements-1-in-cumulus-cells-of-mature-and-immature-oocytes-from-patients-with-polycystic-ovary-syndrome
#7
Kamthorn Pruksananonda, Artisa Wasinarom, Wisan Sereepapong, Porntip Sirayapiwat, Prakasit Rattanatanyong, Apiwat Mutirangura
OBJECTIVE: The long interspersed elements (LINE-1, L1s) are a group of genetic elements found in large numbers in the human genome that can translate into phenotype by controlling genes. Growing evidence supports the role of epigenetic in polycystic ovary syndrome (PCOS). The purpose of this study is to evaluate the DNA methylation levels in LINE-1 in a tissue-specific manner using cumulus cells from patients with PCOS compared with normal controls. METHODS: The study included 19 patients with PCOS and 22 control patients who were undergoing controlled ovarian hyperstimulation...
June 2016: Clinical and Experimental Reproductive Medicine
https://www.readbyqxmd.com/read/27192117/differential-dna-methylation-patterns-of-polycystic-ovarian-syndrome-in-whole-blood-of-chinese-women
#8
Shuxia Li, Dongyi Zhu, Hongmei Duan, Anran Ren, Dorte Glintborg, Marianne Andersen, Vibe Skov, Mads Thomassen, Torben Kruse, Qihua Tan
As a universally common endocrinopathy in women of reproductive age, the polycystic ovarian syndrome is characterized by composite clinical phenotypes reflecting the contributions of reproductive impact of ovarian dysfunction and metabolic abnormalities with widely varying symptoms resulting from interference of the genome with the environment through integrative biological mechanisms including epigenetics. We have performed a genome-wide DNA methylation analysis on polycystic ovarian syndrome and identified a substantial number of genomic sites differentially methylated in the whole blood of PCOS patients and healthy controls (52 sites, false discovery rate < 0...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/27056885/comprehensive-analysis-of-genome-wide-dna-methylation-across-human-polycystic-ovary-syndrome-ovary-granulosa-cell
#9
Jiawei Xu, Xiao Bao, Zhaofeng Peng, Linlin Wang, Linqing Du, Wenbin Niu, Yingpu Sun
Polycystic ovary syndrome (PCOS) affects approximately 7% of the reproductive-age women. A growing body of evidence indicated that epigenetic mechanisms contributed to the development of PCOS. The role of DNA modification in human PCOS ovary granulosa cell is still unknown in PCOS progression. Global DNA methylation and hydroxymethylation were detected between PCOS' and controls' granulosa cell. Genome-wide DNA methylation was profiled to investigate the putative function of DNA methylaiton. Selected genes expressions were analyzed between PCOS' and controls' granulosa cell...
May 10, 2016: Oncotarget
https://www.readbyqxmd.com/read/26975253/epigenetic-and-transcriptional-alterations-in-human-adipose-tissue-of-polycystic-ovary-syndrome
#10
Milana Kokosar, Anna Benrick, Alexander Perfilyev, Romina Fornes, Emma Nilsson, Manuel Maliqueo, Carl Johan Behre, Antonina Sazonova, Claes Ohlsson, Charlotte Ling, Elisabet Stener-Victorin
Genetic and epigenetic factors may predispose women to polycystic ovary syndrome (PCOS), a common heritable disorder of unclear etiology. Here we investigated differences in genome-wide gene expression and DNA methylation in adipose tissue from 64 women with PCOS and 30 controls. In total, 1720 unique genes were differentially expressed (Q < 0.05). Six out of twenty selected genes with largest expression difference (CYP1B1, GPT), genes linked to PCOS (RAB5B) or type 2 diabetes (PPARG, SVEP1), and methylation (DMAP1) were replicated in a separate case-control study...
March 15, 2016: Scientific Reports
https://www.readbyqxmd.com/read/26908643/the-loss-of-imprinted-dna-methylation-in-mouse-blastocysts-is-inflicted-to-a-similar-extent-by-in-vitro-follicle-culture-and-ovulation-induction
#11
M D Saenz-de-Juano, K Billooye, J Smitz, E Anckaert
STUDY HYPOTHESIS: Does in vitro follicle culture (IFC) have an effect on maintenance of imprinted DNA methylation in preimplantation mouse embryos? STUDY FINDING: We report similar alterations in the methylation pattern of H19 imprinted maternally expressed transcript (H19), small nuclear ribonucleoprotein polypeptide N (Snrpn) and mesoderm specific transcript (Mest) imprinted genes in mouse blastocysts obtained after ovulation induction and IFC. Furthermore, we observed no differences in the gene expression of maternal effect proteins related with imprinting maintenance between superovulated in vivo grown or IFC oocytes...
June 2016: Molecular Human Reproduction
https://www.readbyqxmd.com/read/26305227/systems-genetics-reveals-the-functional-context-of-pcos-loci-and-identifies-genetic-and-molecular-mechanisms-of-disease-heterogeneity
#12
Michelle R Jones, Meredith A Brower, Ning Xu, Jinrui Cui, Emebet Mengesha, Yii-Der I Chen, Kent D Taylor, Ricardo Azziz, Mark O Goodarzi
Genome wide association studies (GWAS) have revealed 11 independent risk loci for polycystic ovary syndrome (PCOS), a common disorder in young women characterized by androgen excess and oligomenorrhea. To put these risk loci and the single nucleotide polymorphisms (SNPs) therein into functional context, we measured DNA methylation and gene expression in subcutaneous adipose tissue biopsies to identify PCOS-specific alterations. Two genes from the LHCGR region, STON1-GTF2A1L and LHCGR, were overexpressed in PCOS...
August 2015: PLoS Genetics
https://www.readbyqxmd.com/read/26185601/fetal-programming-of-polycystic-ovary-syndrome
#13
REVIEW
Esra Bahar Gur, Muammer Karadeniz, Guluzar Arzu Turan
Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects up to 6.8% of reproductive age women. Experimental research and clinical observations suggest that PCOS may originate in the very early stages of development, possibly even during intrauterine life. This suggests that PCOS is either genetically-transmitted or is due to epigenetic alterations that develop in the intrauterine microenvironment. Although familial cases support the role of genetic factors, no specific genetic pattern has been defined in PCOS...
July 10, 2015: World Journal of Diabetes
https://www.readbyqxmd.com/read/25956362/genome-wide-screen-of-ovary-specific-dna-methylation-in-polycystic-ovary-syndrome
#14
Ying-Ying Yu, Cui-Xiang Sun, Yin-Kun Liu, Yan Li, Li Wang, Wei Zhang
OBJECTIVE: To compare genome-wide DNA methylation profiles in ovary tissue from women with polycystic ovary syndrome (PCOS) and healthy controls. DESIGN: Case-control study matched for age and body mass index. SETTING: University-affiliated hospital. PATIENT(S): Ten women with PCOS who underwent ovarian drilling to induce ovulation and 10 healthy women who were undergoing laparoscopic sterilization, hysterectomy for benign conditions, diagnostic laparoscopy for pelvic pain, or oophorectomy for nonovarian indications...
July 2015: Fertility and Sterility
https://www.readbyqxmd.com/read/25823942/epigenetic-pattern-changes-in-prenatal-female-sprague-dawley-rats-following-exposure-to-androgen
#15
Yanjie Xia, Shanmei Shen, Xinlin Zhang, Zhantao Deng, Zou Xiang, Hongwei Wang, Long Yi, Qian Gao, Yong Wang
Androgen excess is generally considered to be one of the major characteristics of polycystic ovary syndrome (PCOS). Evidence from both clinical research and animal studies has revealed that this syndrome may have fetal origins, with epigenetics being proposed as the underlying mechanism. Our PCOS rat model induced by prenatal administration of 3mg testosterone from Embryonic Day (E) 16 to E19 showed polycystic ovaries, irregular oestrous cycles and endocrine disorders in adulthood. The methylation status of 16, 8 and 4 cytosine-phosphate-guanine (CpG) sites in the promoter regions of the androgen receptor (Ar), cytochrome P450 family 11, subfamily A, polypeptide 1 (Cyp11a1) and cytochrome P450, family 17, subfamily A, polypeptide 1 (Cyp17a1) genes, respectively, were measured by pyrosequencing...
March 31, 2015: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/25575948/lactonase-activity-and-status-of-paraoxonase-1-in-chinese-women-with-polycystic-ovarian-syndrome
#16
Yujin Zhang, Hongwei Liu, Jin He, Kelei Xu, Huai Bai, Ying Wang, Feng Zhang, Jinxia Zhang, Li Cheng, Ping Fan
OBJECTIVE: To study the relationship between the lactonase activities and status of paraoxonase 1 (PON1) and its association with the PON1 genetic polymorphisms in women with polycystic ovarian syndrome (PCOS). DESIGN: A case-control study. METHODS: A total of 455 PCOS patients and 441 control women were included in this study. The lactonase activities and concentrations of PON1 were assayed using 5-thiobutyl butyrolactone (TBBL) and 7-O-diethylphosphoryl-3-cyano-4-methyl-7-hydroxycoumarin (DEPCyMC) respectively...
April 2015: European Journal of Endocrinology
https://www.readbyqxmd.com/read/25150387/genome-wide-identification-of%C3%A2-aberrantly-methylated-promoters-in%C3%A2-ovarian-tissue-of-prenatally-androgenized-rats
#17
Duojia Zhang, Jing Cong, Huanhuan Shen, Qi Wu, Xiaoke Wu
OBJECTIVE: To identify aberrantly methylated candidate genes that are involved in the development of polycystic ovary syndrome (PCOS). DESIGN: Animal model. SETTING: University-affiliated laboratory. ANIMAL(S): Sprague-Dawley rats. INTERVENTION(S): The prenatally androgenized (PNA) rat model was established. Pregnant rats were treated with daily SC injections of T propionate during late gestation, and their female offspring were studied as adults...
November 2014: Fertility and Sterility
https://www.readbyqxmd.com/read/25051372/genome-wide-dna-methylation-and-gene-expression-patterns-provide-insight-into-polycystic-ovary-syndrome-development
#18
Xiu-Xia Wang, Jing-Zan Wei, Jiao Jiao, Shu-Yi Jiang, Da-Hai Yu, Da Li
Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women. However, the epigenetic mechanism involved in PCOS progression remains largely unknown. Here, combining the DNA methylation profiling together with transcriptome analysis, we showed that (i) there were 7929 differentially methylated CpG sites (β > 0.1, P < 0.05) and 650 differential transcripts (fold change > 1.5, P < 0.005) in PCOS compared to normal ovaries; (ii) 54 genes were identified with methylated levels that were correlated with gene transcription in PCOS; and (iii) there were less hypermethylated sites, but many more hypomethylated sites residing in CpG islands and N_Shore in PCOS...
August 30, 2014: Oncotarget
https://www.readbyqxmd.com/read/25015958/lower-limb-veins-are-thicker-and-vascular-reactivity-is-decreased-in-a-rat-pcos-model-concomitant-vitamin-d3-treatment-partially-prevents-these-changes
#19
Szabolcs Várbíró, Levente Sára, Péter Antal, Anna Monori-Kiss, Anna-Mária Tőkés, Emil Monos, Rita Benkő, Noémi Csibi, Maria Szekeres, Robert Tarszabo, Agnes Novak, Péter Paragi, György L Nádasy
Polycystic ovary syndrome (PCOS) causes vascular damage to arteries; however, there are no data for its effect on veins. Our aim was to clarify the effects of dihydrotestosterone (DHT)-induced PCOS both on venous biomechanics and on pharmacological reactivity in a rat model and to test the possible modulatory role of vitamin D3 (vitD). PCOS was induced in female Wistar rats by DHT treatment (83 μg/day, subcutaneous pellet). After 10 wk, the venous biomechanics, norepinephrine (NE)-induced contractility, and acetylcholine-induced relaxation were tested in saphenous veins from control animals and from animals treated with DHT or DHT with vitD using pressure angiography...
September 15, 2014: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/24992182/early-embryonic-androgen-exposure-induces-transgenerational-epigenetic-and-metabolic-changes
#20
Ning Xu, Angela K Chua, Hong Jiang, Ning-Ai Liu, Mark O Goodarzi
Androgen excess is a central feature of polycystic ovary syndrome (PCOS), which affects 6% to 10% of young women. Mammals exposed to elevated androgens in utero develop PCOS-like phenotypes in adulthood, suggesting fetal origins of PCOS. We hypothesize that excess androgen exposure during early embryonic development may disturb the epigenome and disrupt metabolism in exposed and unexposed subsequent generations. Zebrafish were used to study the underlying mechanism of fetal origins. Embryos were exposed to androgens (testosterone and dihydrotestosterone) early at 26 to 56 hours post fertilization or late at 21 to 28 days post fertilization...
August 2014: Molecular Endocrinology
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