Objetivos: O presente estudo teve como objetivo comparar a frequência das contrações uterinas em gestações gemelares em uso da progesterona natural e de placebo. Método: Estudo randomizado, duplo-cego, placebo controlado, realizado no período de 01 de junho de 2007 a 31 de outubro de 2013. Participaram do estudo 341 gestantes, com 170 randomizadas no grupo progesterona e 171 no grupo placebo. Todas as gestantes realizaram exame de tocografia no período de 24 a 34 semanas e 6 dias, com duração de trinta minutos, a cada três semanas. A contração uterina foi definida como uma elevação da linha de base com amplitude acima de 5 mm e duração mínima de trinta segundos. Na comparação da frequência das contrações uterinas entre os grupos, nas diferentes idades gestacionais, utilizou-se o teste t de Student. O modelo de análise GEE - modelo generalizado de equações de estimação - foi utilizado na comparação, entre os grupos, da frequência das contrações uterinas em relação à idade gestacional no parto, e também na avaliação da interação da frequência das contrações uterinas com a medida do colo uterino e a corionicidade. Resultados: As características epidemiológicas e gerais das gestantes foram semelhantes nos dois grupos. A frequência média das contrações uterinas diferiu entre os grupos apenas na 34ª semana (P = 0,005), com frequência maior de contrações no grupo progesterona (4,81±3,24) em relação ao grupo placebo (2,73 ± 2,06). Não houve diferença significativa na comparação da frequência média das contrações uterinas e a idade gestacional no parto (< 28 sem, < 32 sem, < 34 sem e < 37 semanas) entre os grupos. Não foi observada interação da frequência das contrações uterinas com a medida do colo uterino ou com a corionicidade da gestação, em relação aos grupos progesterona ou placebo. Conclusão: O uso da progesterona natural não interfere na frequência das contrações uterinas nas gestações gemelares abaixo de 34 semanas gestacionais / Objectives: The aim of this study was to comparate uterine contraction frequency in twin pregnancies in use of natural progesterone and placebo. Methods: Randomized, double-blind, placebo-controlled study, conducted between June 1, 2007 to October 31, 2013. The study included 341 twin pregnancies, with 170 randomized in the progesterone group and 171 in the placebo group. All pregnancies had uterine contraction registration by tocodinamometry every three weeks, during 30 minutes between 24 to 34 weeks and 6 days. Uterine contraction was defined as an amplitude greater than 5 mm, from baseline registration, and a duration longer than 30 seconds. Comparison of contraction frequency between the groups at different gestational ages was examined using the parametric student t test. The model GEE - generalized estimating equation model - was used in the comparison, between the groups, the uterine contraction frequency according gestational age at delivery, and also for evaluating the interaction of the frequency contractions with cervical length and chorionicity. Results: Epidemiological and general characteristics of the pregnant woman were similar in both groups. At the 34 weeks, was only gestational age that presented difference (P = 0.005) in the mean uterine contraction frequency between progesterone (4.81 ± 3.24) and placebo (2.73 ± 2.06) groups. No difference in the mean uterine contraction frequency was observed between progesterone and placebo groups in relation to gestational age at delivery. Cervical length measurement and chorionicity did not influence the uterine contraction frequency according to progesterone or placebo. Conclusion: The use of natural progesterone in twin pregnancies does not affect the uterine contraction frequency before 34 weeks gestation

Liu Yuet Man. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (leaves 165-191). / Abstracts in English and Chinese. / Acknowledgement --- p.i / Abstract --- p.iii / Abbreviations --- p.vi / Chapter CHAPTER 1 --- INTRODUCTION --- p.1 / Chapter 1.1 --- Incidences and Prevalence --- p.2 / Chapter 1.2 --- Anatomy of Uterus and its Support Mechanism --- p.3 / Chapter 1.3 --- Pathophysiology of Uterine Prolapse --- p.5 / Chapter 1.4 --- Classification of Uterine Prolapse --- p.6 / Chapter 1.5 --- Etiology of Uterine Prolapse --- p.7 / Chapter 1.6 --- Treatment of Uterine Prolapse --- p.12 / Chapter 1.6.1 --- Conservative Treatment --- p.12 / Chapter 1.6.2 --- Surgical Treatment --- p.13 / Chapter 1.7 --- Molecular Basis of Uterine Prolapse --- p.14 / Chapter 1.7.1 --- Collagen Metabolism --- p.15 / Chapter 1.7.2 --- Extracellular Matrix Metabolism --- p.16 / Chapter 1.7.3 --- Advanced Glycation End-products --- p.18 / Chapter 1.7.4 --- Estrogen and Estrogen Receptors --- p.19 / Chapter 1.8 --- Gene Expression Profiling of Uterine Prolapse --- p.22 / Chapter 1.9 --- Microarray Gene Expression Profiling Analysis --- p.24 / Chapter 1.9.1 --- Types of Microarray --- p.26 / Chapter 1.9.2 --- Comparison of Oligonucleotide and cDNA Arrays --- p.31 / Chapter 1.10 --- Quantitative Real-time PCR --- p.32 / Chapter 1.10.1 --- Principle of TaqMan Real-time PCR --- p.32 / Chapter 1.10.2 --- Other Types of Real-time PCR --- p.33 / Chapter 1.11 --- Project Aims --- p.34 / Chapter 1.12 --- Significance of Study --- p.35 / Chapter CHAPTER 2 --- MATERIALS AND METHODS --- p.37 / Chapter 2.1 --- Materials --- p.37 / Chapter 2.1.1 --- Patients --- p.37 / Chapter 2.1.2 --- Cardinal Ligament Specimen --- p.38 / Chapter 2.2 --- Methods --- p.39 / Chapter 2.2.1 --- Homogenization of Cardinal Ligament Tissues --- p.39 / Chapter 2.2.2 --- Total RNA extraction --- p.39 / Chapter 2.2.3 --- Oligonucleotide Microarray --- p.41 / Chapter 2.2.3.1 --- Two-cycle cDNA Synthesis --- p.41 / Chapter 2.2.3.2 --- Cleanup of Double-stranded cDNA --- p.45 / Chapter 2.2.3.3 --- Synthesis of Biotin-labeled cRNA --- p.45 / Chapter 2.2.3.4 --- Cleanup and Quantification of Biotin-labeled cRNA --- p.46 / Chapter 2.2.3.5 --- Fragmenting the cRNA for Target Preparation --- p.47 / Chapter 2.2.3.6 --- Target Hybridization --- p.47 / Chapter 2.2.3.7 --- "Array Washing, Staining and Scanning" --- p.48 / Chapter 2.2.3.8 --- Statistical Analysis of Microarray Data --- p.49 / Chapter 2.2.4 --- Quantitative Real-time Polymerase Chain Reaction --- p.52 / Chapter 2.2.4.1 --- Primers and Probes --- p.52 / Chapter 2.2.4.2 --- Reverse Transcription --- p.53 / Chapter 2.2.4.3 --- Plate Setup --- p.53 / Chapter 2.2.4.4 --- Real-time PCR Reaction Mixture Setup --- p.54 / Chapter 2.2.4.5 --- Statistical Analysis of Real-time PCR Data --- p.54 / Chapter CHAPTER 3 --- RESULTS --- p.56 / Chapter 3.1 --- Microarray Gene Expression Data Analysis --- p.57 / Chapter 3.1.1 --- Unsupervised Gene Selection --- p.57 / Chapter 3.1.2 --- Supervised Gene Selection --- p.59 / Chapter 3.1.2.1 --- Gene Expression Profiles Distinguish Cardinal Ligament with Uterine Prolapse from Control and Identify Differentially Expressed Genes --- p.59 / Chapter 3.1.2.2 --- Gene Expression Profiles Distinguish Cardinal Ligament with Different Degrees of Uterine Prolapse from Control and Identify Differentially Expressed Genes --- p.72 / Chapter 3.1.2.3 --- Gene Expression Profiles Distinguish Cardinal Ligament with Third-degree Prolapse from First-degree Prolapse and Identify Differentially Expressed Genes --- p.92 / Chapter 3.2 --- Validation of Microarray Data by Quantitative Real-time PCR --- p.96 / Chapter 3.2.1 --- Fold Change of Candidate Genes --- p.97 / Chapter 3.2.2 --- Correlation Between Microarray and Quantitative Real-time PCR Results --- p.102 / Chapter CHAPTER 4 --- DISCUSSIONS --- p.103 / Chapter 4.1 --- Global Gene Expression Profiling using Oligonucleotide Microarray --- p.103 / Chapter 4.1.1 --- Advantages of using Affymetrix GeneChipR Microarray for Gene Expression Profiling --- p.103 / Chapter 4.1.2 --- Microarray analysis software --- p.105 / Chapter 4.1.2.1 --- DNA-Chip Analyzer Software --- p.105 / Chapter 4.1.2.2 --- Comparison of Statistical Methods for Analysis of A ffymetrix GeneChipRMicroarray Data --- p.108 / Chapter 4.2 --- Validation of Microarray Data --- p.111 / Chapter 4.2.1 --- Advantages of using Quantitative Real-time PCR for mRNA Quantification --- p.111 / Chapter 4.3 --- Microarray Gene Expression Data Analysis --- p.115 / Chapter 4.3.1 --- Unsupervised Gene Selection --- p.115 / Chapter 4.3.2 --- Supervised Gene Selection --- p.115 / Chapter 4.3.2.1 --- Gene Expression Profiles Distinguish Cardinal Ligament with Uterine Prolapse from Control and Identify Differentially Expressed Genes --- p.115 / Chapter 4.3.2.2 --- Gene Expression Profiles Distinguish Cardinal Ligament with Different Degrees of Uterine Prolapse from Control and Identify Differentially Expressed Genes --- p.118 / Chapter 4.3.2.3 --- Gene Expression Profiles Distinguish Cardinal Ligament with Third-degree Prolapse from First-degree Prolapse and Identify Differentially Expressed Genes --- p.120 / Chapter 4.4 --- Potential Genes for Further Studies in Uterine Prolapse --- p.120 / Chapter 4.5 --- Implications of This Study --- p.157 / Chapter 4.6 --- Limitations of This Study --- p.160 / Chapter CHAPTER 5 --- CONCLUSIONS --- p.162 / Chapter CHAPTER 6 --- FUTURE PROSPECT --- p.164 / REFERENCES --- p.165

Tam On Yi Ann. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (leaves 138-152). / Abstracts in English and Chinese. / ABSTRACT --- p.I / ACKNOWLEDGMENTS --- p.VI / ABBREVIATIONS --- p.VIII / LIST OF FIGURES --- p.X / LIST OF TABLES --- p.XI / CONTENTS --- p.XII / Chapter Chapter One: --- Introduction --- p.1 / Chapter 1.1 --- History of human papillomavirus --- p.2 / Chapter 1.2 --- Biology of human papillomavirus --- p.4 / Chapter 1.2.1 --- Classification --- p.4 / Chapter 1.2.2 --- Genome structure --- p.5 / Chapter 1.2.3 --- Properties of gene products --- p.6 / Chapter 1.2.3.1 --- El gene --- p.6 / Chapter 1.2.3.2 --- E2 gene --- p.7 / Chapter 1.2.3.3 --- E4 gene --- p.7 / Chapter 1.2.3.4 --- E5 gene --- p.7 / Chapter 1.2.3.5 --- E6 gene --- p.7 / Chapter 1.2.3.6 --- E7 gene --- p.8 / Chapter 1.2.3.7 --- LI and L2 genes --- p.9 / Chapter 1.2.4 --- Latent and lytic life cycle --- p.9 / Chapter 1.2.5 --- Host specificity --- p.10 / Chapter 1.2.6 --- Site of infection --- p.11 / Chapter 1.2.7 --- Clinical manifestations --- p.11 / Chapter 1.2.8 --- Mode of infection --- p.12 / Chapter 1.2.9 --- Detection method --- p.13 / Chapter 1.2.9.1 --- DNA hybridization --- p.13 / Chapter 1.2.9.2 --- DNA amplification methods --- p.15 / Chapter 1.2.9.3 --- Hybrid capture assay --- p.16 / Chapter 1.2.9.4 --- Other DNA detection methods --- p.17 / Chapter 1.2.9.5 --- Serology --- p.18 / Chapter 1.3 --- Biology of cervical intraepithelial neoplasia and cervical cancer --- p.19 / Chapter 1.3.1 --- Grading of severity of cervical neoplasia --- p.20 / Chapter 1.3.2 --- Treatment of cervical intraepithelial lesions --- p.22 / Chapter 1.3.3 --- Prognosis after treatment --- p.22 / Chapter 1.4 --- Epidemiology of cervical cancer --- p.23 / Chapter 1.4.1 --- Global burden of disease --- p.23 / Chapter 1.4.2 --- Local burden of disease --- p.23 / Chapter 1.4.2.1 --- Incidence --- p.23 / Chapter 1.4.2.2 --- Mortality --- p.24 / Chapter 1.4.2.3 --- Age distribution --- p.24 / Chapter 1.4.2.4 --- Trends of incidence and mortality --- p.25 / Chapter 1.4.2.5 --- Morbidity --- p.25 / Chapter 1.4.2.6 --- International comparison --- p.25 / Chapter 1.5 --- Aetiology and risk factors --- p.26 / Chapter 1.5.1 --- Human papillomavirus infection --- p.26 / Chapter 1.5.2 --- Number of sexual partners --- p.26 / Chapter 1.5.3 --- Age of first sexual intercourse --- p.27 / Chapter 1.5.4 --- Presence of other sexually-transmitted diseases --- p.28 / Chapter 1.5.5 --- Cigarette smoking --- p.29 / Chapter 1.5.6 --- Diet --- p.30 / Chapter 1.5.7 --- Oral contraceptives --- p.30 / Chapter 1.5.8 --- Parity --- p.31 / Chapter 1.5.9 --- Age --- p.32 / Chapter 1.5.10 --- Socio-economic status --- p.32 / Chapter 1.6 --- Malignant transformation of human papillomavirus infection --- p.33 / Chapter 1.7 --- Primary prevention of cervical cancer - vaccine for human papillomavirus --- p.38 / Chapter 1.7.1 --- Classification of vaccine for human papillomavirus --- p.38 / Chapter 1.7.2 --- Human papillomavirus vaccination combined with human papillomavirus screening --- p.39 / Chapter 1.8 --- Secondary prevention of cervical cancer --- p.40 / Chapter 1.8.1 --- Cytology screening --- p.40 / Chapter 1.8.2 --- Detection of human papillomavirus --- p.41 / Chapter 1.9 --- Human papillomavirus and cervical cancer --- p.43 / Chapter 1.9.1 --- Risk association between cervical cancer and human papillomavirus infection --- p.43 / Chapter 1.9.2 --- World-wide prevalence of human papillomavirus types in cervical cancer --- p.43 / Chapter 1.9.3 --- Human papillomavirus prevalence in China and Hong Kong --- p.44 / Chapter Chapter Two: --- Materials and Methods --- p.49 / Chapter 2.1 --- Ethics approval --- p.50 / Chapter 2.2 --- Sample management --- p.50 / Chapter 2.2.1 --- Sample collection --- p.50 / Chapter 2.2.2 --- Sample storage and labelling --- p.50 / Chapter 2.3 --- DNA extraction --- p.51 / Chapter 2.3.1 --- Physical extraction 226}0ؤ heating --- p.51 / Chapter 2.3.2 --- Chemical extraction - Qiagen kit extraction --- p.51 / Chapter 2.4 --- Polymerase chain reaction --- p.53 / Chapter 2.4.1 --- Controls for polymerase chain reaction --- p.53 / Chapter 2.4.2 --- Beta-globin polymerase chain reaction --- p.53 / Chapter 2.4.3 --- HPV 52-specific human papillomavirus polymerase chain reaction --- p.56 / Chapter 2.4.4 --- Consensus human papillomavirus L1 open-reading frame polymerase chain reaction --- p.57 / Chapter 2.4.4.1 --- GP5+/6+ polymerase chain reaction --- p.57 / Chapter 2.4.4.2 --- MY09/11 polymerase chain reaction --- p.60 / Chapter 2.4.4.3 --- PGMY09/11 polymerase chain reaction --- p.63 / Chapter 2.5 --- Genotyping of human papillomavirus --- p.65 / Chapter 2.5.1 --- Restriction fragment length polymorphism --- p.65 / Chapter 2.5.2 --- Reverse line-blot hybridization --- p.67 / Chapter 2.6 --- Sequencing --- p.69 / Chapter 2.6.1 --- Sequencing for HPV genotyping --- p.69 / Chapter 2.6.2 --- Sequencing of HPV 52 E6 and E7 genes --- p.69 / Chapter 2.7 --- Statistical analysis --- p.70 / Chapter Chapter Three --- Study I 226}0ؤ Comparison of Three HPV DNA Detection Methods --- p.71 / Chapter 3.1 --- Objective --- p.72 / Chapter 3.2 --- Study plan --- p.72 / Chapter 3.3 --- Results --- p.74 / Chapter 3.3.1 --- Study population --- p.74 / Chapter 3.3.2 --- Optimisation of polymerase chain reactions --- p.74 / Chapter 3.3.3 --- Method 1: GP5+/6+ PCR followed by cycle sequencing --- p.76 / Chapter 3.3.4 --- Method 2: MY09/11 PCR followed by restriction fragment length polymorphism --- p.76 / Chapter 3.3.5 --- Method 3: PGMY09/11 PCR followed by reverse line-blot hybridization --- p.77 / Chapter 3.3.6 --- Prevalence and genotype distribution of human papillomavirus infection in cervical cancer patients --- p.81 / Chapter 3.3.7 --- Detection of multiple infections --- p.81 / Chapter 3.3.8 --- Sensitivity of the detection methods --- p.82 / Chapter 3.3.9 --- Comparison of prevalence rates of human papillomavirus genotypes --- p.82 / Chapter 3.3.10 --- Comparison of genotype distribution in Hong Kong cervical cancer patients with other geographic regions --- p.83 / Chapter 3.3.11 --- Follow-up investigation of GP5+/6+ primer binding site in HPV 52 --- p.84 / Chapter 3.4 --- Discussion --- p.91 / Chapter Chapter Four --- Study II - Post-treatment Follow-up Study on Patients with High-grade Cervical Lesions --- p.95 / Chapter 4.1 --- Objective --- p.96 / Chapter 4.2 --- Study plan --- p.96 / Chapter 4.3 --- Results --- p.97 / Chapter 4.3.1 --- Study population --- p.97 / Chapter 4.3.2 --- The prevalence and genotype distribution of human papillomavirus infection before treatment --- p.98 / Chapter 4.3.3 --- Persistent human papillomavirus infection --- p.99 / Chapter 4.3.4 --- Risk-factors associated with persistent human papillomavirus infection --- p.99 / Chapter 4.3.4.1 --- Excision margin status --- p.99 / Chapter 4.3.4.2 --- Multiple human papillomavirus infections --- p.99 / Chapter 4.4 --- Discussion --- p.108 / Chapter 4.4.1 --- Prevalence and genotype distribution of human papillomavirus in high-grade cervical neoplasia --- p.108 / Chapter 4.4.2 --- Risk factors for cervical intraepithelial neoplasia recurrence --- p.110 / Chapter Chapter Five --- Study III - Investigation of Human Papillomavirus 52 Sequence Variation --- p.115 / Chapter 5.1 --- Objective --- p.116 / Chapter 5.2 --- Study plan --- p.116 / Chapter 5.3 --- Results --- p.117 / Chapter 5.3.1 --- Study population --- p.117 / Chapter 5.3.2 --- Nucleotide sequence variations --- p.119 / Chapter 5.3.2.1 --- Human papillomavirus 52 E6 open-reading frame --- p.119 / Chapter 5.3.2.2 --- Human papillomavirus 52 E7 open-reading frame --- p.123 / Chapter 5.3.2.3 --- Comparison of nucleotide sequence variations in HPV 52 E6 and E7 open-reading frame --- p.128 / Chapter 5.4 --- Discussion --- p.134 / References --- p.137

Do ponto de vista da produtividade, a fertilidade é um dos parâmetros de maior importância em um rebanho bovino comercial e esta é influenciada por vários fatores, entre eles estão as condições do trato reprodutivo das fêmeas e a qualidade do sêmen utilizado. O influxo de células inflamatórias no local da deposição do sêmen logo após a inseminação artificial (IA) pode ser intensificada na presença de maior número de espermatozoides lesados durante a IA, caracterizando uma endometrite. Este estudo foi conduzido em três experimentos. Com o objetivo de comparar os métodos de colheita de material endometrial por escova ginecológica (EU) e lavado uterino (LU), bem como a interferência destes procedimentos na hemodinâmica uterina, foi proposto o Experimento 01, onde pode-se constatar que ambas as técnicas permitem o recolhimento de amostras em quantidade e qualidade suficiente para contagem, e que a porcentagem de células polimorfonucleares obtidas pela técnica LU foi superior a EU. Maior fluxo sanguíneo das artérias uterinas foi encontrado no momento de 4 horas após a realização de LU, sugerindo que este influencia na resposta vascular inflamatória. Para avaliar o efeito da LU após a IA em Tempo Fixo (IATF) na fertilidade dos animais, executou-se o Experimento 02 e constatou-se que não há diferença no índice de prenhez entre os animais submetidos ou não à LU, demonstrando que a técnica não interfere na taxa de fertilidade. Com o intuito de investigar a interferência da qualidade do sêmen na fertilidade, resposta inflamatória e hemodinâmica uterina, foi proposto o Experimento 03, onde foi possível observar influência da qualidade do sêmen sobre a taxa de prenhez, verificou-se maior porcentagem de vacas prenhes quando inseminadas com sêmen com maiores percentuais de espermatozoides apresentando integridade das membranas plasmática e acrossomal e função mitocondrial (PIAIC). Notou-se ainda a ocorrência de endometrite em 65,3 % dos animais, os quais apresentaram taxa de prenhez inferior aos que não apresentaram inflamação. Pode-se concluir que a qualidade do sêmen e a endometrite interferem na taxa de fertilidade bovina. / When productivity is taking into account, fertility is one of the most important parameters in a commercial herd. It is influenced by several factors, especially by the conditions of the female reproductive tract and the quality of the semen used. The influx of inflammatory cells at the site of semen deposition after artificial insemination (AI) can be intensified by the deposition of a greater number of dead spermatozoa during AI, which characterized endometritis. This study was conducted in three different experiments. In order to compare the methods of collection of endometrial sampling by swab using a gynecological brush (GB) or uterine flushing (UF), as well as the interference of these procedures in uterine hemodynamics, we designed experiment 01. Our results reveal that both techniques allow collecting samples with good quality and sufficient quantity to be counted; moreover, the average percentage of polymorphonuclear cells obtained by UF was greater compared to those obtained by GB. It may be noted that the increased blood flow was observed in samples collected four hours after the UF procedure, suggesting that it may have an influence on the vascular inflammatory response. To evaluate the effect of uterine flushing after AIFT on animal fertility we designed the experiment 02. Our results revealed that there is no statistical difference in pregnancy rates between flushed and non flushed animals, showing that the UF does not interfere with fertility rate. Experiment 03 was designed in order to assess the inflammatory response induced by different qualities of semen and their interference on uterine hemodynamic and fertility. There was an influence of semen quality on pregnancy rates: higher percentage of pregnancy was found in the group of cows inseminated with semen with plasma and acrossome membrane integrity and mitochondrial function (PIAIC). Endometritis was noticed in 65.3% of the cows and these animals presented lower pregnancy rate compared to those that did not show an inflammatory response. We concluded that semen quality and endometritis interferes with fertility rate in bovine species.

Objetivos: O presente estudo teve como objetivo comparar a frequência das contrações uterinas em gestações gemelares em uso da progesterona natural e de placebo. Método: Estudo randomizado, duplo-cego, placebo controlado, realizado no período de 01 de junho de 2007 a 31 de outubro de 2013. Participaram do estudo 341 gestantes, com 170 randomizadas no grupo progesterona e 171 no grupo placebo. Todas as gestantes realizaram exame de tocografia no período de 24 a 34 semanas e 6 dias, com duração de trinta minutos, a cada três semanas. A contração uterina foi definida como uma elevação da linha de base com amplitude acima de 5 mm e duração mínima de trinta segundos. Na comparação da frequência das contrações uterinas entre os grupos, nas diferentes idades gestacionais, utilizou-se o teste t de Student. O modelo de análise GEE - modelo generalizado de equações de estimação - foi utilizado na comparação, entre os grupos, da frequência das contrações uterinas em relação à idade gestacional no parto, e também na avaliação da interação da frequência das contrações uterinas com a medida do colo uterino e a corionicidade. Resultados: As características epidemiológicas e gerais das gestantes foram semelhantes nos dois grupos. A frequência média das contrações uterinas diferiu entre os grupos apenas na 34ª semana (P = 0,005), com frequência maior de contrações no grupo progesterona (4,81±3,24) em relação ao grupo placebo (2,73 ± 2,06). Não houve diferença significativa na comparação da frequência média das contrações uterinas e a idade gestacional no parto (< 28 sem, < 32 sem, < 34 sem e < 37 semanas) entre os grupos. Não foi observada interação da frequência das contrações uterinas com a medida do colo uterino ou com a corionicidade da gestação, em relação aos grupos progesterona ou placebo. Conclusão: O uso da progesterona natural não interfere na frequência das contrações uterinas nas gestações gemelares abaixo de 34 semanas gestacionais / Objectives: The aim of this study was to comparate uterine contraction frequency in twin pregnancies in use of natural progesterone and placebo. Methods: Randomized, double-blind, placebo-controlled study, conducted between June 1, 2007 to October 31, 2013. The study included 341 twin pregnancies, with 170 randomized in the progesterone group and 171 in the placebo group. All pregnancies had uterine contraction registration by tocodinamometry every three weeks, during 30 minutes between 24 to 34 weeks and 6 days. Uterine contraction was defined as an amplitude greater than 5 mm, from baseline registration, and a duration longer than 30 seconds. Comparison of contraction frequency between the groups at different gestational ages was examined using the parametric student t test. The model GEE - generalized estimating equation model - was used in the comparison, between the groups, the uterine contraction frequency according gestational age at delivery, and also for evaluating the interaction of the frequency contractions with cervical length and chorionicity. Results: Epidemiological and general characteristics of the pregnant woman were similar in both groups. At the 34 weeks, was only gestational age that presented difference (P = 0.005) in the mean uterine contraction frequency between progesterone (4.81 ± 3.24) and placebo (2.73 ± 2.06) groups. No difference in the mean uterine contraction frequency was observed between progesterone and placebo groups in relation to gestational age at delivery. Cervical length measurement and chorionicity did not influence the uterine contraction frequency according to progesterone or placebo. Conclusion: The use of natural progesterone in twin pregnancies does not affect the uterine contraction frequency before 34 weeks gestation

子宮頸癌是女性的主要癌症殺手，而人類乳頭瘤病毒 (HPV) 則是子宮頸癌形成的必要條件之一。HPV16型及HPV18型是全球最普遍的高危型HPV；而另一方面，HPV52及HPV58兩型在東亞地區的流行程度比世界其他地區為高。 / 過往有科學研究顯示HPV病毒載量的高低是引致高度癌前病變的重要決定因素，也有研究指出病毒載量與病變的嚴重程度成正比例，但同時亦有研究指兩者並無關係。HPV基因組可以兩種物理形態存在：游離型及整合型。HPV的E2基因可對E6及E7致癌基因產生重要的調節作用，而當HPV病毒與宿主染色體整合後，可使E2基因斷裂，因而令控制E6及E7致癌基因表達的負反饋基制失效。 / 本研究假設高病毒載量及由HPV基因組整合所造成的E2基因斷裂，並非引致子宮頸癌的僅一途徑。本研究分析了在不同程度的子宮頸細胞病變下，HPV16型、18型、52型及58型的病毒載量及基因整合情況。其中，有關HPV16型的研究部份更深入地探討了E6/7 mRNA的轉錄水平、E2和LCR的序列變異及E2結合位點的甲基化情況，最終希望能找出除了病毒基因整合之外的另一種致癌機理。 / 本研究的結果顯示，在不同HPV型所引致的子宮頸細胞病變中，病毒載體及病變程度之間的關係也存有差異；而根據管家基因的數量來為細胞DNA標準化，對準確分析不同程度子宮頸細胞病變的實驗結果至關重要。本研究的一項重要發現是部份侵襲性癌細胞只含有游離型HPV基因組；而在只含游離HPV基因組的侵襲性子宮頸癌樣本中，有三種E6/E7 mRNA的抄錄本水平與只含整合型基因組的樣本相若，反映在只含游離型HPV基因組的侵襲性子宮頸癌樣本中，E6/ E7 mRNA的表達量亦有上調。最重要的是，此表達量的上調並非由基因整合或E2基因斷裂所引致。 / 在只含有游離型病毒基因組的侵襲性子宮頸癌樣本中，E6及E7致癌基因表達上調的另一種機理，很可能是HPV16啟動區內E2結合位點上的CpG位點出現甲基化。這項觀察解釋及支持了當E2蛋白因結合位點甲基化而失去對E6及E7基因轉錄的抑制功能時，E6及E7致癌蛋白仍能保持高水平，而兩種蛋白產生協同作用，令細胞轉型及出現癌變。總結之言，本實驗也肯定了HPV整合並非導致子宮頸癌形成的唯一機理。 / Cervical cancer is a major cause of cancer-related death in women worldwide. Human papillomavirus (HPV) is essential, though not sufficient, to cause cervical cancer. HPV16 and HPV18 are the most prevalent high-risk types worldwide, whereas, HPV52 and HPV58 also show a notable higher prevalence in East Asia than in other parts of the world. / Studies have suggested that HPV viral load is an important determinant for the development of high-grade lesions. While some studies observed a positive correlation between viral load and disease severity, others have reported no association. The HPV genome can exist in two physical forms, episomal or integrated. The E2 gene, encoded by HPV has an important role in the regulation of E6 and E7 viral oncogenes. When HPV integrates into the host chromosome, it may result in disruption of the E2 gene thereby its control on the expression of the E6 and E7. / The hypothesis for this study was that high viral load and disruption of E2 gene associated with integration of HPV into the host genome was not the only pathway leading to cervical cancer development. In this study, the viral load and integration profile for HPV types 16, 18, 52 and 58 among different severity of cervical lesions were analyzed. Further detailed studies were performed on HPV16 with emphases on E6/E7 mRNA transcript levels, E2 and LCR sequence variation and the methylation status of two E2 binding sites. The ultimate aim was to determine what other alternative mechanisms exist apart from viral integration to drive the oncogenicity of HPV that lead to the development of cervical cancer. / The results showed that the relationship between viral load and disease varied between different HPV types and that normalization of cellular DNA input using a housekeeping gene was crucial for accurate interpretation among different cervical lesion grades. A key finding from this study was that a substantial proportion of invasive cervical carcinomas were found to contain the purely episomal form of the HPV genome. The levels of the three E6/E7 mRNA transcripts species in invasive cervical carcinomas containing the pure episomal form of the viral genome were found to be similar to those with pure integrated forms. This observation suggested that invasive cervical carcinoma samples containing the episomal form of the HPV genome were also mediated by the up-regulated E6/E7 mRNA expression. More importantly, this up-regulation in E6/E7 mRNA expression did not depend on integration and disruption of the E2 gene. / The alternative mechanism that up-regulated of the expression of E6 and E7 oncogene found in invasive cervical carcinoma samples harbouring the episomal form of the viral genome was likely to be a consequence of methylation of CpG sites in the two E2 binding sites at the promoter region of HPV16. This observation explained and supported that the repressive role of E2 on E6 and E7 transcriptional regulation was abolished due to methylation of the E2 binding sites, and that a sustained level of the E6 and E7 oncoproteins was maintained, working in synergy in cell transformation and in carcinogenesis. These observations confirmed the hypothesis that HPV integration was not the only mechanism leading to the development of cervical cancer. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Cheung, Lai Ken Jo. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 233-248). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese. / Acknowledgements --- p.I / Abstract of thesis --- p.IV / 論文摘要 --- p.VII / Publications --- p.IX / Contents --- p.X / Figures --- p.XV / Tables --- p.XVIII / Abbreviations --- p.XIX / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Cervical Cancer --- p.2 / Chapter 1.1.1 --- Cervical Cytology Screening --- p.3 / Chapter 1.1.2 --- Classification System for Cervical Squamous Cell Dysplasia --- p.4 / Chapter 1.1.3 --- Histological Grading of Cervical Lesions --- p.6 / Chapter 1.1.4 --- Development of Cervical Cancer --- p.6 / Chapter 1.2 --- Structure of HPV --- p.7 / Chapter 1.1.1 --- HPV Genome Organization --- p.8 / Chapter 1.1.2 --- The E1 Protein --- p.10 / Chapter 1.1.3 --- The E2 Protein --- p.10 / Chapter 1.1.4 --- The E4 Protein --- p.13 / Chapter 1.1.5 --- The E5 Protein --- p.13 / Chapter 1.1.6 --- The E6 Protein --- p.14 / Chapter 1.1.7 --- The E7 Protein --- p.14 / Chapter 1.1.8 --- The L1 Protein --- p.15 / Chapter 1.1.9 --- The L2 Protein --- p.16 / Chapter 1.1.10 --- The Long Control Region --- p.17 / Chapter 1.3 --- HPV and Cervical Cancer --- p.19 / Chapter 1.3.1 --- HPV is an Etiological Cause of Cervical Cancer --- p.19 / Chapter 1.3.2 --- Establishment of HPV Infection --- p.20 / Chapter 1.3.3 --- Regulation and Control of HPV Viral Gene Transcription --- p.23 / Chapter 1.3.4 --- Viral Oncogene Expression by Alternative RNA Splicing --- p.23 / Chapter 1.3.5 --- DNA Methylation in Viral Oncogene Expression --- p.24 / Chapter 1.3.6 --- The Roles of E6 and E7 Protein in Cervical Carcinogenesis --- p.26 / Chapter Chapter 2 --- Controversies and Hypothesis --- p.33 / Chapter 2.1 --- Controversies in Mechanism of Cervical Carcinogenesis --- p.34 / Chapter 2.1.1 --- Viral Integration and Risk of Cervical Cancer Development --- p.34 / Chapter 2.1.2 --- Viral Load and Risk of Cervical Cancer Development --- p.35 / Chapter 2.2 --- Hypothesis of Study --- p.37 / Chapter 2.2.1 --- Study Design --- p.38 / Chapter Chapter 3 --- Materials and Methods --- p.41 / Chapter 3.1 --- Patient Recruitment and Sample Preparation --- p.42 / Chapter 3.1.1 --- Study subject recruitment --- p.42 / Chapter 3.1.2 --- Collection of cytology samples --- p.43 / Chapter 3.1.3 --- Collection of cervical biopsy samples --- p.44 / Chapter 3.2 --- Nucleic Acid Extraction and Preparation --- p.44 / Chapter 3.2.1 --- Extraction of DNA from cervical cytology samples --- p.44 / Chapter 3.2.2 --- Extraction of DNA from cervical biopsy samples --- p.45 / Chapter 3.2.3 --- Extraction of RNA from cervical cytology samples --- p.45 / Chapter 3.2.4 --- Extraction of RNA from cervical biopsy samples --- p.46 / Chapter 3.3 --- Detection and Genotyping of Human Papillomavirus --- p.46 / Chapter 3.4 --- Determination of Viral Load using Real-Time Polymerase Chain Reaction --- p.47 / Chapter 3.4.1 --- Optimization of HPV16, 18, 52 and 58 E7 real-time PCR --- p.48 / Chapter 3.4.2 --- Optimization of housekeeping gene real-time PCR --- p.50 / Chapter 3.4.3 --- Determination of HPV16, 18, 52 and 58 viral load --- p.50 / Chapter 3.5 --- Determination of HPV Genome Physical Status --- p.53 / Chapter 3.5.1 --- HPV E2 gene primer design --- p.53 / Chapter 3.5.2 --- Optimization of HPV16, 18, 52 and 58 E2 Real-time PCR --- p.56 / Chapter 3.5.3 --- Determination of the HPV genome physical status --- p.59 / Chapter 3.6 --- Evaluation of Housekeeping Genes for Normalization of Viral Gene Expression --- p.62 / Chapter 3.6.1 --- Optimization of housekeeping gene real-time PCR --- p.62 / Chapter 3.6.2 --- Quantitation of RNA and DNase treatment --- p.66 / Chapter 3.6.3 --- cDNA synthesis from the extracted RNA --- p.67 / Chapter 3.6.4 --- Detection of five housekeeping gene levels from cervical cytology samples by real-time PCR --- p.67 / Chapter 3.6.5 --- Data analyses --- p.68 / Chapter 3.7 --- Quantitation of HPV16 mRNA Transcripts --- p.69 / Chapter 3.7.1 --- Preparation of RNA from CaSki cells --- p.69 / Chapter 3.7.2 --- Amplification of mRNA transcripts from CaSki cells --- p.69 / Chapter 3.7.3 --- Amplification of artificial mRNA transcript E6*II --- p.73 / Chapter 3.7.4 --- Gel purification of mRNA transcript amplicons --- p.73 / Chapter 3.7.5 --- Cloning of E6 mRNA transcripts --- p.74 / Chapter 3.7.6 --- Confirmation of the mRNA transcript inserts --- p.74 / Chapter 3.8 --- Quantitation HPV16 E6 mRNA Transcript Levels Using Real-Time PCR --- p.79 / Chapter 3.8.1 --- mRNA transcript primer and probe design --- p.79 / Chapter 3.8.2 --- Optimization of real-time PCR for the detection of mRNA transcripts --- p.82 / Chapter 3.8.3 --- Determination of mRNA transcript levels from invasive carcinomas --- p.83 / Chapter 3.8.4 --- Normalization of mRNA transcript expression with a housekeeping gene --- p.84 / Chapter 3.9 --- Sequence Variation of the HPV16 E2 and Long Control Region --- p.84 / Chapter 3.9.1 --- Identification of sequence variation of the E2 gene --- p.84 / Chapter 3.9.2 --- Identification of sequence variation of the long control region --- p.87 / Chapter 3.1 --- Detection of Methylation Status of E2BS1 and E2BS2 on the LCR using Pyrosequencing --- p.87 / Chapter 3.10.1 --- Bisulfite DNA conversion --- p.87 / Chapter 3.10.2 --- Amplification of E2 binding site regions on the LCR --- p.88 / Chapter 3.10.3 --- Purification of PCR product prior to pyrosequencing --- p.92 / Chapter 3.10.4 --- Quantitation of methylation using pyrosequencing --- p.92 / Chapter Chapter 4 --- Results --- p.93 / Chapter Hypothesis 1 --- p.94 / Chapter Results of Study Part: 1 --- p.95 / Chapter 4.1 --- Human Papillomavirus Type 16 Viral Load and Genome Physical Status --- p.96 / Chapter 4.1.1 --- E7 viral load --- p.96 / Chapter 4.1.2 --- Viral genome physical status --- p.100 / Chapter 4.1.3 --- E2 disruption site --- p.105 / Chapter 4.2 --- Human Papillomavirus Type 18 Viral Load and Genome Physical Status --- p.107 / Chapter 4.2.1 --- E7 viral load --- p.107 / Chapter 4.2.2 --- Viral genome physical status --- p.110 / Chapter 4.2.3 --- E2 disruption site --- p.113 / Chapter 4.2.4 --- Infection status --- p.116 / Chapter 4.2.5 --- Adeno/adenosquamous carcinoma versus squamous cell carcinoma --- p.119 / Chapter 4.3 --- Human Papillomvirus Type 52 Viral Load and Genome Physical Status --- p.120 / Chapter 4.3.1 --- E7 viral load --- p.120 / Chapter 4.3.2 --- Viral genome physical status --- p.123 / Chapter 4.3.3 --- E2 disruption site --- p.126 / Chapter 4.3.4 --- Infection status --- p.129 / Chapter 4.4 --- Human Papillomavirus Type 58 Viral Load and Genome Physical Status --- p.131 / Chapter 4.4.1 --- E7 viral load --- p.131 / Chapter 4.4.2 --- Viral genome physical status --- p.133 / Chapter 4.4.3 --- E2 disruption site --- p.134 / Chapter 4.4.4 --- Infection status --- p.137 / Chapter 4.5 --- Summary of Study Part 1: --- p.140 / Chapter Hypothesis 2 --- p.141 / Chapter Results of Study Part 2: --- p.142 / Chapter 4.6 --- Housekeeping Gene mRNA Expression Level --- p.143 / Chapter 4.6.1 --- Expression levels across different grades of cervical lesion --- p.143 / Chapter 4.6.2 --- Expression stability of housekeeping genes --- p.145 / Chapter 4.7 --- Summary of Study Part 2: --- p.149 / Chapter Results of Study Part: 3 --- p.150 / Chapter 4.8 --- HPV16 mRNA Transcript Expression Level --- p.151 / Chapter 4.8.1 --- HPV16 viral genome physical status --- p.151 / Chapter 4.8.2 --- HPV16 E2 disruption site --- p.151 / Chapter 4.8.3 --- Expression level of E6/E7 mRNA transcripts --- p.155 / Chapter 4.8.4 --- Expression level of E6/E7 mRNA transcripts and viral genome physical status --- p.157 / Chapter 4.8.5 --- Expression level of E6/E7 mRNA transcripts and E2 gene disruption status --- p.161 / Chapter 4.9 --- Summary of Study Part 3: --- p.163 / Chapter Hypothesis 3 --- p.165 / Chapter Results of Study Part 4: --- p.166 / Chapter 4.1 --- HPV 16 E2 Gene Sequence Variation --- p.167 / Chapter 4.10.1 --- Sequence variation of E2 gene --- p.167 / Chapter 4.10.2 --- Sequence variation and viral genome physical status --- p.168 / Chapter 4.10.3 --- Sequence variation in the E2 binding sites --- p.169 / Chapter 4.10.4 --- Sequence variations of E2 in HPV16 cancer derived cell lines --- p.170 / Chapter 4.11 --- HPV16 Long Control Region Sequence Variation --- p.174 / Chapter 4.11.1 --- Sequence variation of LCR --- p.174 / Chapter 4.11.2 --- Sequence variation and viral genome physical status --- p.175 / Chapter 4.11.3 --- Sequence variation in E2 binding sites --- p.176 / Chapter 4.11.4 --- Sequence variation of LCR in HPV16 cancer derived cell lines --- p.176 / Chapter 4.12 --- Summary of Study Part 4: --- p.183 / Chapter Hypothesis 4 --- p.185 / Chapter 4.13 --- Methylation Status of E2 Binding Sites --- p.187 / Chapter 4.13.1 --- Proportion methylation in E2 binding sites --- p.187 / Chapter 4.13.2 --- Methylation in invasive carcinomas according to the viral genome physical status --- p.191 / Chapter 4.14 --- Summary of Study Part 5: --- p.195 / Chapter Chapter 5 --- Discussion --- p.196 / Chapter 5.1 --- Viral Load --- p.197 / Chapter 5.2 --- Viral Integration --- p.200 / Chapter 5.2.1 --- HPV16 Viral Load and Physical Status --- p.201 / Chapter 5.2.2 --- HPV18 Viral Load and Physical Status --- p.204 / Chapter 5.2.3 --- HPV52 Viral Load and Physical Status --- p.207 / Chapter 5.2.4 --- HPV58 Viral Load and Physical Status --- p.210 / Chapter 5.2.5 --- Viral Load and Physical Status Summary --- p.214 / Chapter 5.3 --- HPV16 E6/E7 mRNA Transcript and Genome Physical Status --- p.215 / Chapter 5.4 --- HPV16 E2 Sequence Variation and Genome Physical Status --- p.218 / Chapter 5.5 --- HPV16 LCR Sequence Variation and Genome Physical Status --- p.222 / Chapter 5.6 --- Methylation of HPV16 E2 Binding Sites and Genome Physical Status --- p.225 / Chapter 5.7 --- Conclusions --- p.230 / Chapter 5.8 --- Implication of Current Findings and Future Work --- p.231 / References --- p.233

Diss. (sammanfattning) Stockholm : Karol. inst., 2005. / Härtill 5 uppsatser.

Licentiatvhandling (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 2 uppsatser.

Do ponto de vista da produtividade, a fertilidade é um dos parâmetros de maior importância em um rebanho bovino comercial e esta é influenciada por vários fatores, entre eles estão as condições do trato reprodutivo das fêmeas e a qualidade do sêmen utilizado. O influxo de células inflamatórias no local da deposição do sêmen logo após a inseminação artificial (IA) pode ser intensificada na presença de maior número de espermatozoides lesados durante a IA, caracterizando uma endometrite. Este estudo foi conduzido em três experimentos. Com o objetivo de comparar os métodos de colheita de material endometrial por escova ginecológica (EU) e lavado uterino (LU), bem como a interferência destes procedimentos na hemodinâmica uterina, foi proposto o Experimento 01, onde pode-se constatar que ambas as técnicas permitem o recolhimento de amostras em quantidade e qualidade suficiente para contagem, e que a porcentagem de células polimorfonucleares obtidas pela técnica LU foi superior a EU. Maior fluxo sanguíneo das artérias uterinas foi encontrado no momento de 4 horas após a realização de LU, sugerindo que este influencia na resposta vascular inflamatória. Para avaliar o efeito da LU após a IA em Tempo Fixo (IATF) na fertilidade dos animais, executou-se o Experimento 02 e constatou-se que não há diferença no índice de prenhez entre os animais submetidos ou não à LU, demonstrando que a técnica não interfere na taxa de fertilidade. Com o intuito de investigar a interferência da qualidade do sêmen na fertilidade, resposta inflamatória e hemodinâmica uterina, foi proposto o Experimento 03, onde foi possível observar influência da qualidade do sêmen sobre a taxa de prenhez, verificou-se maior porcentagem de vacas prenhes quando inseminadas com sêmen com maiores percentuais de espermatozoides apresentando integridade das membranas plasmática e acrossomal e função mitocondrial (PIAIC). Notou-se ainda a ocorrência de endometrite em 65,3 % dos animais, os quais apresentaram taxa de prenhez inferior aos que não apresentaram inflamação. Pode-se concluir que a qualidade do sêmen e a endometrite interferem na taxa de fertilidade bovina. / When productivity is taking into account, fertility is one of the most important parameters in a commercial herd. It is influenced by several factors, especially by the conditions of the female reproductive tract and the quality of the semen used. The influx of inflammatory cells at the site of semen deposition after artificial insemination (AI) can be intensified by the deposition of a greater number of dead spermatozoa during AI, which characterized endometritis. This study was conducted in three different experiments. In order to compare the methods of collection of endometrial sampling by swab using a gynecological brush (GB) or uterine flushing (UF), as well as the interference of these procedures in uterine hemodynamics, we designed experiment 01. Our results reveal that both techniques allow collecting samples with good quality and sufficient quantity to be counted; moreover, the average percentage of polymorphonuclear cells obtained by UF was greater compared to those obtained by GB. It may be noted that the increased blood flow was observed in samples collected four hours after the UF procedure, suggesting that it may have an influence on the vascular inflammatory response. To evaluate the effect of uterine flushing after AIFT on animal fertility we designed the experiment 02. Our results revealed that there is no statistical difference in pregnancy rates between flushed and non flushed animals, showing that the UF does not interfere with fertility rate. Experiment 03 was designed in order to assess the inflammatory response induced by different qualities of semen and their interference on uterine hemodynamic and fertility. There was an influence of semen quality on pregnancy rates: higher percentage of pregnancy was found in the group of cows inseminated with semen with plasma and acrossome membrane integrity and mitochondrial function (PIAIC). Endometritis was noticed in 65.3% of the cows and these animals presented lower pregnancy rate compared to those that did not show an inflammatory response. We concluded that semen quality and endometritis interferes with fertility rate in bovine species.

The overall objective of the research presented in this dissertation was to assess exposure to endocrine disrupting chemicals (EDCs), polychlorinated biphenyls (PCBs), phthalates, and bisphenol A (BPA) in the general population and evaluate their associations with adverse reproductive health effects, including cancers, in women. Given the proven contribution of unopposed estrogens to the risk for endometrial neoplasia or breast cancer, renewed health concerns have aroused about estrogen mimicking EDCs found in food, personal care products or as environmental contaminants. Our meta-analysis showed that exposure to estrogen mimicking PCBs increased summary risk of breast cancer and endometriosis. We further evaluated the relationship between endometriosis and breast cancer, and EDCs using a bioinformatics method. Our bioinformatics approach was able to identify genes with the potential to be involved in interaction with PCB, phthalates and BPA that may be important to the development of breast cancer and endometriosis. Therefore, we hypothesized that exposure to EDCs such as PCBs, phthalates, and BPA, results in adverse reproductive health effects in women. Using subject data and biomarkers available from the Center for Disease Controls National Health and Nutrition Examination Survey database we conducted a cross-sectional study of EDCs in relation to self-reported history of endometriosis, uterine leiomyomas, breast cancer, cervical cancer, ovarian cancer, and uterine cancer. Significantly higher body burdens of PCBs were found in women diagnosed with breast cancer, ovarian cancer, and uterine cancer compared to women without cancer. PCB 138 was significantly associated with breast cancer, cervical cancer, and uterine cancer, while PCBs 74 and 118 were significantly associated with ovarian cancer. The sum of dioxin-like PCBs were significantly associated with ovarian cancer (OR of 2.02, 95% CI: 1.06-3.85) and the sum of non-dioxin-like PCBs were significantly associated with uterine cancer (OR of 1.12, 95%CI: 1.03-1.23). Significantly higher body burdens of PCBs were also found in women diagnosed with endometriosis and uterine leiomyomas. Documenting the exposure to EDCs among the general U.S. population, and identifying agents associated with reproductive toxicity have the potential to fill research gaps and facilitate our understanding of the complex role environmental chemicals play in producing toxicity in reproductive organs.