Orientador: Paulo Cesar Giraldo / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-11T12:50:20Z (GMT). No. of bitstreams: 1 Sbroggio_AdrianaMagrinRivera_D.pdf: 1067710 bytes, checksum: ee257ad4d227b8c5795865af0aac269d (MD5) Previous issue date: 2008 / Resumo: A cada ano o número de histerectomias vem aumentando gradativamente em todo o mundo. Para muitas mulheres a perda do útero poderá causar impacto emocional, despertando sentimentos de perda, inutilidade e destituição da condição feminina. Objetivo: Avaliar a autopercepção das mulheres submetidas à histerectomia relativa às modificações corpóreas, afetivas e sexuais. Pacientes e métodos: Cento e sessenta e quatro mulheres histerectomizadas há mais de três meses e até cinco anos - de diferentes níveis socioeconômicos - foram entrevistadas através de um questionário semi-estruturado. O trabalho abordou questões relativas à autopercepção das alterações corpóreas, afetivas e sexuais acerca da retirada do útero com a finalidade de verificar se o ato cirúrgico poderia associar-se a essas alterações. A análise de associação entre as variáveis foi realizada através dos testes de X2 e Exato de Fisher. O trabalho foi avaliado e aprovado pela Comissão de Ética e Pesquisa. Resultados: A média de idade das mulheres foi de 47,6 (±6,9) anos; 49,4% eram da religião católica; 59,1% foram submetidas à histerectomia por mioma e 17,7% das mulheres tinham menos de dois filhos. Menos de 10% das mulheres submetidas à histerectomia relataram insatisfação quanto ao procedimento, associada a possíveis transtornos sexuais e corporais. Não houve diferença significativa da autopercepção quanto a modificações afetivas e sexuais nas mulheres de diferentes níveis socioeconômicos. Apesar disso, constatou-se que a autopercepção corpórea de ¿rejuvenescimento¿ foi estatisticamente significativa. Conclusão: A satisfação de ser histerectomizada parece suplantar os medos e receios da ausência do útero e o fator socioeconômico parece não interferir quanto à percepção das mudanças corporais, sexuais e afetivas após a histerectomia. Palavras-chave: histerectomia, mulher, sexualidade / Abstract: Every year the number of hysterectomies gradually increases all over the world. For many women the uterus loss may cause emotional impact, awakening loss feelings, feelings of uselessness and of the feminine condition deprivation. Objective: To evaluate the self-perception of women submitted to hysterectomy in relation to corporal, affective and sexual modifications. Patients and methods: One hundred and sixty-four women who have undergone hysterectomies more than three months ago up to five years, among different socioeconomic levels, were interviewed using a semi-structured questionnaire. The research approached matters of self-perception in relation to corporal, affective and sexual alterations, concerning the uterus removal, aiming to examine if the surgical act may had been associated with these alterations. The association analysis among variables was accomplished through X2 and Fisher¿s exact tests. The research was evaluated and approved by the Ethics and Research Commission. Results: The women¿s average age was 47.6 (±6.9) years; 49.4% were Catholics; 59.1% were submitted to hysterectomy due to myoma and 17.7% had less than two children. Less than 10% of these women submitted to hysterectomy showed dissatisfaction towards the procedure associated to eventual sexual and corporal disorders. There weren¿t significant differences of self-perception related to affective and sexual modifications on women of different socioeconomic levels. In spite of this, it was observed that the corporal self-perception of ¿rejuvenation¿ was statistically significant. Conclusion: The satisfaction in undergoing hysterectomy seems to overcome the fears and concerns regarding the uterus absence and the socioeconomic factor seems to not interfere in the perception of corporal, sexual and affective changes after hysterectomy. Key-words: hysterectomy, woman, sexuality / Doutorado / Ciencias Biomedicas / Doutor em Tocoginecologia

Durante o puerpério há muita incidência de doenças reprodutivas acarretando aumento do intervalo entre partos, bem como diminuição na taxa de concepção. A endometrite é uma enfermidade puerperal que se caracteriza por um processo inflamatório superficial do endométrio. Com o intuito de se obter novas ferramentas diagnósticas não invasivas, precisas e que proporcionam resultados precoce à reprodução, faz-se uso da ultrassonografia convencional associada a ferramenta Doppler que fornece informações em tempo real sobre a arquitetura vascular e os aspectos hemodinâmicos dos vasos em diversos órgãos. Este estudo tem por objetivo descrever, através da ultrassonografia Doppler, as alterações hemodinâmicas no útero de fêmeas bovinas causadas pela endometrite. Avaliou-se o trato reprodutivo feminino de vacas entre 25 a 35 dias pós-parto utilizando a vaginoscopia, ultrassonografia convencional e Doppler, além de citologia e exame microbiológico em 89 vacas Holandesas sendo 33 sadias (controle) e 56 com endometrite diagnosticadas por citologia (saudáveis <10% de polimorfonucleares). Os resultados obtidos destacam-se a que animais com endometrite apresentavam aumento de cérvix (p=0,04), e de útero representado pelo corno esquerdo (p=0,02). Porém não foi observado diferença quando comparado os escore de condição corporal (ECC). Quanto a ultrassonografia notou-se que animais com fluido intrauterino (FIU) e conteúdo heterogêneo intrauterino (CHIU) tinham endometrite (p<0,0001), além de correlação com a presença de Trueperella pyogenes e leveduras. Com o modo cores do Doppler obteve-se a vascularização de mesométrio (p=0,004) e endométrio (p=0,025) associada aendometrite. Entretanto não foi observado diferença estatística nas medidas do Doppler espectral (índice de resistividade, pulsatilidade e fluxo sanguíneo). Portanto a busca de novas técnicas, menos invasivas e de rápido resultado, como a ultrassonografia Doppler, podem fornecer respostas satisfatórias quanto a evolução de alterações uterinas e com isso associar os resultados à precocidade reprodutiva. / During the puerperium period there is a high incidence of reproductive diseases resulting in increased calving interval and decrease in conception rate. The endometritis is a postpartum disease that is characterized by a superficial inflammation of endometrium. With the aim to obtain new non-invasive and accurate diagnostic tools, that provide early results in reproduction, it is possible to be used the conventional ultrasound associated to Doppler that provides real time information about vascular architecture and hemodynamic aspects of vessels in several organs. This study aims to describe, through Doppler ultrasound, hemodynamic changes in the uterus of cows caused by endometritis. Were evaluated the female reproductive tract of 89 Holstein cows between 25 to 35 days postpartum using vaginoscopy, conventional ultrasound and Doppler, as well as cytology and microbiological examination. From the 89 animals that were studied, 33 were healthy (control) and 56 with endometritis diagnosed by cytology (healthy <10% polymorphonuclear). The obtained results show that animals with endometritis had increase in cervix (p = 0.04) and the uterus represented by left uterine horn (p = 0.02). However, it was not detected difference when compared the body condition score (BCS). About the ultrasound was noted that animals with intrauterine fluid (IUF) and intrauterine heterogeneous content (IUHC) had endometritis (p <0.0001) correlation with the presence of Trueperella pyogenes and yeasts. With the color Doppler mode it was possible to obtain the vascularization of mesometrium (p = 0.004) and endometrium (p = 0.025) associated with endometritis. However, it was not observed statistical difference in the measurements of the spectral Doppler (resistance index, pulsatility and blood flow). Therefore, the search for new techniques, less invasive and fast result, as the Doppler ultrasound can provide satisfactory answers as the evolution of uterine changes and thereby associate the results to the reproductive precocity.

Em bovinos , as flutuações nas concentrações de estradiol (E2) e progesterona ( P4) que ocorrem em torno do estro modulam a expressão gênica do endométrio, a composição histotrofo, o desenvolvimento do concepto e assim afetam o resultado da prenhez. Durante o ciclo estral, ações endócrinas bem orquestradas afetam o endométrio bovino (BAUERSACHS et al., 2005). No presente trabalho, a hipótese sustentada é que alterações endócrinas associadas ao crescimento e ovulação de folículos de diferentes tamanhos modulam a distribuição espacial das transcrições no trato reprodutivo de vacas da raça Nelore. O crescimento folicular de vacas Nelore multíparas e não lactantes foi farmacologicamente manipulado a fim de gerar grupos com folículos pré-ovulatórios e subsequente corpo lúteo (ou seja, diferentes ambientes endócrinos periovulatórios) grande (FG CLG; n = 6) ou pequeno (FP CLP, n = 6). Os animais foram abatidos, sete dias após a indução da ovulação e fragmentos das regiões anterior, média e posterior de ambos os cornos uterinos e da vagina foram coletados para a avaliação de expressão gênica por PCR quantitativo. A expressão gênica foi normalizada utilizando os genes referência ciclofilina A e beta actina, como indicado pelo software GeNorm. Os dados foram analisados utilizando-se o procedimento PROC MIXED do SAS (versão 9.2; Instituto SAS) em dois modelos independentes. O primeiro modelo incluiu os efeitos de grupo (FG CLG e FP CLP), lado do corno uterino (ipsolateral ou contralateral ao ovário contendo o CL) e sua interação, o segundo modelo incluiu os efeitos de grupo, região (anterior, médio e posterior) do corno ipsolateral e suas interações. Vacas do grupo FP CLP apresentou maiores folículos pré-ovulatórios e concentrações de E2 durante proestro e maiores CL e níveis de P4 no diestro inicial, quando comparados com os do grupo FP CLP. Animais do grupo FP CLP apresentaram uma maior abundância de transcritos que codificam o receptor de E2 (ESR2; 130%), a aldo-ceto redutase família 1, membro C4 (AKR1C4; 232%), a lipoproteína lipase (LPL; 116%), o carreador de soluto família 2, membro 1 (SLC2A1; 24%) e inibidor da peptidase da serina, subtipo A, membro 14 (SERPINA14; 75%). Por outro lado, a expressão de genes que codificam o receptor de P4 e receptor de oxitocina foi regulada positivamente no tecido endometrial do grupo FP CLP (36 % e 966 %, respectivamente). Além disso, a abundância da transcrição desse genes foi maior no corno contralateral ao CL. Além disso, a região anterior do corno uterino ipsolateral apresentou aumentada expressão de PGR, ESR2, LPL, SLC2A1 e SERPINA14 em comparação com a região posterior. Com exceção da OXTR que apresentou interação grupo e lado, não houve interações grupo por lado ou região. Não houve efeito de grupo sobre a expressão de qualquer um dos genes na vagina. Em conclusão, o presente estudo mostrou que o padrão de expressão de genes específicos em resposta variou quanto a grupo e entre as regiões do trato reprodutivo de fêmeas bovinas. No entanto, os distintos ambientes endócrino periovulatórios não afetaram a distribuição regional de transcritos. / In cattle, fluctuations of progesterone (P4) and estradiol (E2) concentrations that occur around estrus modulate endometrial gene expression, histotroph composition, conceptus development and, thereby affect pregnancy outcome. During the estrous cycle, well-orchestrated endocrine actions affect the bovine endometrium (BAUERSACHS et al., 2005). In the present work, we hypothesized that endocrine changes associated with growth and ovulation of follicles of different sizes modulate the spatial distribution of transcripts in the reproductive tract of Nellore cows. The follicular growth of multiparous non-lactating Nelore cows was pharmacologically manipulated in order to generate groups with large (LF LCL; n=6) or small (SF SCL; n=6) preovulatory follicles and subsequent corpus luteum (i.e., different periovulatory endocrine milieus). Cows were slaughtered seven days after the induction of ovulation and fragments from the anterior, middle and posterior regions from both uterine horns and the vagina were collected. Gene expression assessment was performed by quantitative PCR. Gene expression was normalized using cyclophilin A and actin, beta as reference genes, as indicated by the GeNorm software. Data were analysed using the PROC MIXED procedure of SAS (Version 9.2; SAS Institute) in two independent models. The first model included the effects of group (LF LCL and SF SCL), side of the uterine horn (ipsilateral or contralateral to the ovary containing the CL) and interaction and the second model included the effects of group, region of the ipsilateral horn (anterior, middle and posterior) and interaction. Cows in the LF LCL group presented larger preovulatory follicles and E2 concentrations during proestrus and larger CL and P4 levels during early diestrus when compared to animals from SF SCL group. Animals in the LF LCL group had a greater abundance of transcripts coding the estrogen receptor (ESR2; 130%), aldo-keto reductase family 1, member C4 (AKR1C4; 232%), lipoprotein lipase (LPL; 116%), solute carrier family 2, member 1 (SLC2A1; 24%) and serpin peptidase inhibitor, clade A member 14 (SERPINA14; 75%). Conversely, the expression of genes coding the progesterone receptor and oxytocin receptor was upregulated in the SFSCL endometrial tissue (36% and 966% respectively). Furthermore, transcript abundance of the later genes was observed in the contralateral horn. In addition, the anterior region of the ipsilateral horn showed increased expression of PGR, ESR2, LPL, SLC2A1 and SERPINA14 compared to the posterior region. Except for a group by side interaction for the expression of OXTR, there were no group by region or group by side interactions. There was no effect of group on the expression of any of the genes in the vagina. In conclusion, our study showed that the expression pattern of specific genes varied in response to group and among regions of the female reproductive tract. However, distinct endocrine periovulatory milieus did no affect regional distribution of transcripts.

No description available.

The cAMP-second messenger hypothesis for β-adrenoceptor-induced relaxation of uterine smooth muscle was tested in high-K+ depolarized rat uterus. At 10⁻⁸ M concentration, Isoproterenol, a β -adrenergic agonist, could cause relaxation of the depolarized uterus without Increasing tissue cAMP levels. Further, although increases in cAMP levels were associated, in some cases, with -isoproterenol (10⁻⁸ M or 10⁻⁴ M)-Induced relaxation, there was no quantitative correlation between the Increases in cAMP and relaxation. Pretreatment of the tissue with a phosphodiesterase Inhibitor, RO 20-1724 (10⁻⁴ M), did not potentiate the relaxation response to Isoproterenol. These results suggested that there Is no simple cause and effect relationship between β -adrenoceptor-Induced Increases in cAMP levels and relaxation in uterine smooth muscle. The dissociation between cAMP and relaxation found ln the present study was also extended to cGMP, since no changes in cGMP levels were observed with isoproterenol-induced relaxation. It is generally accepted that the ionic environment of the cell affects the cellular responses of the tissue. It was demonstrated that hlgh-K*" depolarization of uterine smooth muscle caused an impairment of the ability of isoproterenol to induce cAMP accumulation. This was found to be related to Increased Ca++-Influx known to occur during depolarization. This Is because pretreatment of the tissue with 10⁻⁵M D-600, an Inhibitor of Ca++-lnflux, restored the stimulation of cAMP by Isoproterenol ln the depolarized muscle to a level similar to that observed ln non-depolarized muscle. Furthermore, there was an Inverse relationship between [ca++] ex in the depolarizing medium (range 0.9 to 7.2 mM) and increases in cAMP produced by isoproterenol (10⁻⁴ M). It was also found that exposure of the rat uterus to a Ca++-deficient solution (Ca++-free with 0.2 mM EGTA) accentuated the Increase of tissue cAMP content produced by isoproterenol (10⁻⁸ M). The studies on ionic interactions demonstrated that the presence of Na+(80 mM) or high Mg++(2.5 mM) in the depolarizing medium could overcome the blockade of lsoproterenol-induced increases in cAMP levels by high-K+ depolarization. The studies on the mechanism of this effect of Na+ on the cAMP response revealed that Na+ exerted this effect probably by reducing the Increase In Ca++-influx occurring during depolarization. A similar type of interaction between Mg++ and Ca++ was also observed. These studies have pointed out a possible regulatory role of Ca++ in isoproterenol-lnduced Increases in cAMP levels in uterine smooth muscle. Since it was also demonstrated that cAMP Is not an obligatory requirement In order for Isoproterenol to produce relaxation, these data have raised the question as to whether the Increases ln cAMP produced by β-adrenoceptor stimulation Is an event secondary to the changes in Ca++ movements produced by the agonist. The electrophysiological studies showed that isoproterenol (10 M) could inhibit spontaneous contractility of the rat uterus without causing hyperpolarlzation. In hlgh-K+ depolarized muscle, Isoproterenol (10⁻⁶M) produced relaxation without any change in membrane potential. These data suggested that hyperpolarlzation of cell membranes is not a prerequisite for β-adrenoceptor-med-lated relaxation of uterine smooth muscle. / Pharmaceutical Sciences, Faculty of / Graduate

As a result of alcohol consumption being highly prevalent in today’s society, research has been done to investigate the effects of alcohol on the body’s physiological systems. Research has indicated that heavy alcohol consumption is detrimental to the normal structure and function of some organs, especially the liver. However, little research has focused on the effects of chronic alcohol consumption on the female reproductive system. To investigate these effects, the uterine tissues of mice fed an ethanol diet (the NIAAA model also known as the Lieber-DeCarli diet) and mice fed a control diet were compared. The NIAAA model was chosen for this research because it simulates the drinking pattern that is known to cause liver disease in alcoholic hepatitis patients. This is achieved by incorporating both chronic and binge drinking patterns of alcohol consumption. In this study, the mucin layer that lines the endometrial surface of the uterus was analyzed in mice separated into ethanol and control fed groups. The ethanol fed mice were put on the Lieber-DeCarli 5% (v/v) ethanol diet ad libitum for 10-days followed by a single high dose of ethanol (5g/kg) on the 11th day. The control fed mice were placed on an ethanol free isocaloric diet (supplemented with maltose dextrin to match the calories of ethanol). After the 11th day, the mice were sacrificed, and uterine tissues were harvested. The tissues were then embedded in paraffin, sectioned, stained via the Hematoxylin and Eosin (H&E) technique, and examined under a microscope. The thickness of the uterine mucin layer was then measured for each animal and the average thicknesses were calculated. A one-way ANOVA test was employed to compare the mucin thickness between the two groups of animals. The test revealed no statistically significant difference between the thicknesses of the uterine mucin layer in the control and ethanol fed animals (P-value: 0.774).

One of the major healthcare issues found almost worldwide, especially in the United States, is the obesity epidemic. Obesity is known to have deleterious effects on many body/organ systems. C1q TNF-related protein-3 (CTRP3) is effective at preventing high-fat diet-induced fatty liver. With these two factors taken into consideration, this study explores the possible effects of a high caloric diet on the muscle wall of the uterus, i.e., the myometrium, and how over-expression of CTRP3 may modify those effects. We hypothesize that consumption of excessive amounts of fat and sugar will have detrimental effects on the dual layers of the mouse myometrium. For this study, 17 mice were divided into 4 treatment groups: wild type/low fat diet, wild type/high fat diet, CTRP3-overexpressing/low fat diet, and CTRP3-overexpressing/high fat diet. The mice were placed on their respective diets at 7 weeks of age with a feeding duration of 12 weeks. At the conclusion of the feeding protocol, the female reproductive tissues were harvested and fixed in 4% paraformaldehyde and subsequently paraffin embedded. The uterine horns of each mouse were painstakingly paraffin embedded in a vertical position so that cross sections of the uterus could be obtained and measured. These 4µ sections were stained using standard H&E staining techniques and visualized under light microscopy. A randomization grid was utilized to determine measurement locations on the tissue. For each animal, 15 measurements were made of the outer longitudinal layer of the uterine horn, as well as 15 measurements of the inner circular layer, and 15 measurements of the thickness of the two layers combined. Two-way ANOVA was used to determine if any changes seen were statistically significant. At the time of the writing of this abstract, no appreciable differences have been found between the treatment groups, although there will be more data and final statistics completed before the presentation of our findings.

The evolutionary process leading to the emergence of viviparity in Squamata consists of lengthening the period of egg retention in utero coupled with marked reduction in the thickness of the eggshell. We used light microscopy and scanning electron microscopy to study uterine structure during the reproductive cycle of oviparous and viviparous females of the reproductively bimodal Lacerta vivipara. We compared the structure of the uterine shell glands, which secrete components of the eggshell, during preovulatory and early gestation phases of the reproductive cycle and also compared histochemistry of the eggshells. The uterine glands of both reproductive forms undergo considerable growth within a period of a few weeks during folliculogenesis and vitellogenesis preceding ovulation. The majority of the proteinaceous fibers of the shell membrane are secreted early in embryonic development and the uterine glands regress shortly thereafter. This supports previous observations indicating that, in Squamata, secretion of the shell membrane occurs very rapidly after ovulation. The most striking differences between reproductive modes were larger uterine glands at late vitellogenesis in oviparous females, 101 μm compared to 60 μm in viviparous females, and greater thickness of the shell membrane during early gestation in oviparous females (52-73 μm) compared to viviparous females (4-8 μm). Our intraspecific comparison supports the conclusions of previous studies that, prior to ovulation, the uterine glandular layer is less developed in viviparous than in oviparous species, and that this is the main factor accounting for differences in the thickness of the shell membrane of the two reproductive forms of squamates.

This study comprises the ramifications of a diet high in fat and sugar contents that manifest in the uterus. What a clinical setting deems excessive is unfortunately a societal norm in terms of diet. For this reason, it is of a critical nature to investigate the consequences of diets high in sugar and fat contents for the sake of women’s health. Our hypothesis is that consumption of excessive amounts of fat and sugar will have detrimental effects on the muscle layers of the uterus, the myometrium. Since much of the research concerning uterine tissue behavior involves aspects such as pregnancy and fertility assays, this study does not include such facets. The uterine horns of nine high sugar/high fat diet fed mice were collected and transversely sectioned in order to measure the thickness of each uterine layer. At the time of this submission measurements were still being taken and statistical analyses has not yet been completed.

L-arginine is one of the most versatile amino acids due to the fact that it serves as a precursor for many molecules which have important roles in bodily functions including mammalian reproduction. The current studies sought to further examine the role that L-arginine has in mammalian reproduction utilizing both in vivo and in vitro approaches. In the first study, a novel bioluminescent murine pregnancy model was developed to monitor VEGFR2 transcription activity non-invasively in the fetoplacental unit. Secondly, the effect that dietary L-arginine supplementation has during mouse gestation was examined. L-arginine supplementation increased weight gain during the latter third of gestation, total litter size, number of implantation sites, and litter birth weight. Additionally, L-arginine supplementation increased VEGFR2 transcription activity in the fetoplacental unit which may create a more favorable environment for fetal survival. Moreover, the increased number of implantation sites observed suggests an effect of L-arginine at the level of the endometrium. To this end, the effect that L-arginine has on apoptosis and cell proliferation in an established endometrial cell line was examined. The addition of L-arginine at physiological (200 micromolar) and supra-physiological (800 micromolar) concentrations increased cell proliferation , and this effect was achieved through biosynthesis of polyamines and nitric oxide. L-arginine also decreased the proportion of cells that were experiencing mitochondrial mediated apoptosis, and it was observed that this decrease in mitochondrial mediated apoptosis was concurrent with increased phosphorylation of BAD protein, which induces apoptosis when not phosphorylated. The final study examined the ability of porcine uterine epithelial (PUE) cells to synthesize L-arginine from L-citrulline. L-citrulline was able to support PUE cell proliferation in the absence of L-arginine. Additionally, ASS-1 and ASL, L-arginine synthesizing enzymes, were expressed in PUE cells and were regulated by the presence of L-arginine and L-citrulline, respectively. This data would support the hypothesis that PUE cells may be able to convert L-citrulline to L-arginine. Together, the current findings along with the plethora of relevant literature provide further evidence for the role of L-arginine in mammalian reproduction and allow for new questions to be investigated regarding this particular amino acid’s role in mammalian reproduction.