L’apparition de l’obésité et du cancer du sein est influencée par l’exposition aux polluants environnementaux. Ces polluants interfèrent avec le fonctionnement normal de l’organisme causant des modifications dans le comportement cellulaire. Ils peuvent agir chacun seul ou sous forme de cocktail. Dans ce contexte, nous avons choisi trois polluants dans notre projet : le bisphénol A (perturbateur endocrinien), le glyphosate (désherbant) et l’acide okadaïque (toxine marine). Nous avons étudié leur effet seul ou en cocktail sur les cellules de cancer du sein MCF7 et MDA-MB231, les cellules épithéliale mammaire humaine HME1 et les préadipocytes humain HWP. Dans une première partie, nous avons étudié leur effet sur la viabilité cellulaire. L’électrophorèse 2D couplée à MS/MALDI-TOF, le dosage de l’activité des protéines phosphatases ont été menés pour comprendre le mécanisme d’action des polluants sur la viabilité cellulaire. La partie suivante a porté sur la détection et la quantification des polluants dans le milieu de culture afin de déterminer leur voie d’action : extra ou intra cellulaire. Finalement, nous avons étudié l’effet des polluants sur le cycle de vie des adipocytes et la lipogenèse. Également, l’effet de sécrétome des HWP (+/-polluants) sur la viabilité cellulaire des cellules cancéreuses a été étudié. / The development of obesity and breast cancer is influenced by exposure to environmental pollutants. These pollutants interfere with the normal body function causing changes in cells behavior. They can act each alone or as a cocktail. In this context, we have chosen three pollutants in our project : bisphenol A (endocrin disruptor), glyphosate (herbicide), okadaic acid (marin toxine). We have studied their effect of alone or in combination in cellular models : human breast cancer cells MCF7 and MDA-MB 231, human mammary epithelial cells HME1 and human preadipocytes HWP. In the first part, we have studied the effect of pollutants on cells viability. 2D electrophoresis coupled to MS/MALDI-TOF, measurement of proteins phosphatase activity were conducted to understand pollutants action mechanism on cells viability. In the following part we detected and quantified pollutants in culture medium to determine their pathway of action : extra or intra cellular. Finally, we studied the effect of pollutants on adipocytes life cycle and lipogenesis. Also, effect of secretome from HWP (+/- pollutants) on cancer cells viability was studied.

Obesity is a current epidemic in the United States. Greater than one third of adults and nearly one fifth of children are classified as obese (Ogden, 2014). Increased awareness of this problem has triggered interest into the potentially causal agents in our environment. These agents, termed obesogens, are a type of teratogen hypothesized to work during embryonic development by programming offspring to store excess fat. A type of teratogen, obesogens are also typically reprotoxic, affecting germline development and embryonic viability. These noxious teratogens span a variety of different chemical classes including estrogen mimics, metals and metalloids, biocides, and even voluntary exposures like cigarette smoke. The goal of this work is to use the soil nematode, Caenorhabditis elegans to model the reprotoxic and obesogenic events that take place as a result of chronic, low-dose exposure to these agents. C. elegans is especially well suited to this end. The organism has a straightforward biology, a short lifespan on the order of days, and relevant lipid metabolic gene homology to humans. We characterize here the resultant effects on egg-laying, hatching, and embryo viability after chronic parental exposure to obesogens. Through this, we are able to best recapitulate the low-dose exposure for our obesogen screen. Here, chronic, sub-lethal parental exposure to the obesogens screened yielded viable offspring that exhibited increased percentages of body area lipid stained and induced differences in stained lipid localization. Reduced pharyngeal pumping rates in two of our offspring groups highlights the potential for lasting changes on behavioral phenotype as well. Lastly, we employed phylogenetic guided analysis to functionally assess putative C. elegans nuclear hormone receptors (NHRs) to human Peroxisome Proliferator Activated Receptors (PPARs). These human PPARs have implications in lipid metabolism and obesity. We report here novel findings that NHR-85 and SEX-1 may act to repress lipid storage in the nematode, thereby serving as potential homologs of human PPARα. The results presented in this study highlight the lasting effects of chronic parental exposure to noxious environmental teratogens on the function of the reproductive system. Furthermore, the nematode can be used as an in vivo model to screen sublethal doses of these teratogens for their potential to act as obesogens. Bioinformatics guided analysis of C. elegans NHR homologs to human NHRs can continue to yield novel insight on this fat storage and its regulation in the nematode.

Os desreguladores endócrinos, como o bisfenol A (BPA), são compostos encontrados na água em concentrações da ordem de μg.L-1 ou ng.L-1, sendo por isso também denominados micropoluentes. Sua presença, mesmo em baixas concentrações, pode causar prejuízos aos organismos expostos. Neste contexto, o objetivo do presente trabalho foi avaliar a remoção de BPA por membranas de ultrafiltração (UF) e osmose inversa (OI) e por carvão ativado granular (CAG). Essas técnicas têm a vantagem de não gerar subprodutos que também podem ser tóxicos. Nos estudos foram realizados experimentos para remoção do BPA através de membrana PL-1 (celulose regenerada de 1 kDa), Sy-10 (polietersulfona de 10 kDa) e membrana de OI (poliamida) reutilizada, com concentração inicial de 500 μg.L-1 de BPA. Para a membrana Sy-10, foram testados os pHs 7 e 10. Os ensaios de adsorção foram realizados com CAG (1-2mm) em frascos contendo 100 mL da solução de BPA, com 0,5 g de CAG para cada frasco. As variáveis testadas foram pH, tempo de contato e concentração inicial na ordem de mg.L-1. Adicionalmente, foi testada a concentração inicial de 500 μg.L-1 de BPA em experimento de adsorção. Os resultados obtidos mostraram que a capacidade da membrana Sy-10 para remoção de BPA foi superior, chegando a cerca de 90% de remoção, em contraposição aos 20% encontrados para PL-1. A membrana de OI apresentou remoções de cerca de 95%. A influência do pH (7 e 10) na remoção do BPA para a membrana Sy-10 não mostrou-se significativa. Nos ensaios de adsorção, analisando diferentes valores de pH, obteve-se eficiência de 93% para pH 7. Ensaios de variação do tempo de contato com CAG mostraram que o equilíbrio é atingido nos primeiros 10 minutos para a maior concentração e em 40 minutos para a menor concentração testada, de 500 μg.L-1. O estudo do efeito da concentração inicial de BPA na adsorção mostrou que a remoção aumenta com o aumento da concentração inicial do poluente. Conclui-se que tanto a adsorção em CAG quanto membranas são boas alternativas para a remoção de BPA de soluções aquosas. As duas técnicas poderiam ser usadas conjuntamente, sendo que o concentrado do processo com membranas poderia ser submetido à adsorção por CAG. / Endocrine disrupting chemicals, such as bisphenol A (BPA) compounds, are found in water at concentrations of the order of μg.L-1 or ng.L-1 is therefore also known micropollutants. His presence, even at low concentrations, can cause damage to exposed organisms. In this context, the aim of this study was to evaluate the removal of BPA by ultrafiltration (UF) and reverse osmosis (RO) membranes and granular activated carbon (GAC). These techniques have the advantage of not generating by-products can also be toxic. In the studies were performed experiments to remove the BPA by PL-1 (1 kDa regenerated cellulose), Sy-10 (10 kDa polyethersulfone) and RO (polyamide) reused membranes, with initial concentration of 500 μg.L-1 of BPA. For Sy-10 membrane pHs 7 and 10 were tested. The adsorption experiments were carried out with GAC (1-2mm) in flasks containing 100 mL of the BPA solution and 0.5 g of GAC to each vial. The variables tested were pH, contact time and initial concentration on the order of mg.L-1. Additionally, we tested the initial concentration of 500 μg.L-1 of BPA in adsorption experiment. Results showed that the capacity of Sy-10 membrane to remove BPA was higher, reaching approximately 90% removal, as opposed to the 20% found to PL-1. The RO membrane showed removal of about 95%. The influence of pH (7 and 10 ) in the removal of BPA onto the membrane Sy - 10 was not significant. In adsorption tests, analyzing different pH values was obtained efficiency from 93% to pH 7. Testing time variation of contact GAC showed that equilibrium is reached in the first 10 minutes to the largest concentration and 40 minutes to the lowest concentration tested, 500 μg.L-1. The study of the effect of the initial concentration of BPA in the adsorption showed that removal increases with increase in the initial concentration of the pollutant. It was concluded that both the GAC adsorption as membranes are good alternatives for the removal of the BPA aqueous solutions. The two techniques could be used together, with the concentrate from the membrane process could be subjected to adsorption GAC.

Orientador: Everardo Magalhães Carneiro / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-26T17:22:21Z (GMT). No. of bitstreams: 1 Goncalves_LucianaMateus_M.pdf: 1375240 bytes, checksum: fe3cbb519b479a70d1a3fcd2f6fd3b82 (MD5) Previous issue date: 2015 / Resumo: incidência do diabetes mellitus tipo 2 vem crescendo em todo o mundo, e a estimativa para os próximos anos é que continue aumentando. Dentro desse panorama, destacamos estudos relacionados com substâncias classificadas como desreguladores endócrinos, caracterizados tanto por alterar a síntese, liberação e ação de hormônios bem como atuar sobre receptores hormonais. Dentre os desreguladores endócrinos, alguns apresentam potencial obesogênico e diabetogênico, como é o caso do Bisfenol A (BPA). Estudos demonstram que o BPA, substância utilizada na manufatura do plástico policarbonato e resina epóxi, possui ação sobre receptores de estrógeno. Devido sua ampla aplicação em itens utilizados cotidianamente, estamos constantemente expostos ao BPA desde o desenvolvimento fetal. O objetivo desse estudo foi investigar o efeito da exposição de ilhotas pancreáticas de camundongos neonatos ao BPA. Foram utilizadas ilhotas de neonatos (4 a 6 dias de vida) cultivadas por 48 horas com 0,1nM de BPA para avaliar: 1) secreção de insulina; 2) expressão gênica; 3) conteúdo proteico. Os resultados foram analisados pelo teste t-Student, com nível de significância p<0,05. A secreção de insulina induzida por glicose ou solução de KCl 40 mM foi prejudicada nas ilhotas tratadas com BPA. O conteúdo total de insulina, assim como a expressão dos genes da insulina não foram alterados. Houve redução tanto da expressão gênica como do conteúdo proteico de conexina 36 nas ilhotas tratadas. O BPA reduziu a expressão gênica da subunidade beta 2 do canal de cálcio do tipo L e o conteúdo proteico das subunidades kir6.2 e sur1 do canal de potássio ATP-dependente. O conteúdo de vamp2 e sintaxina 1A também foi menor nas ilhotas tratadas. Concluímos que a exposição das ilhotas de neonatos ao BPA na concentração e tempo utilizados promove alterações dos mecanismos moleculares envolvidos na secreção de insulina / Abstract: Type 2 diabetes is increasing worldwide. Recently, studies have shown the diabetogenic effects of some chemical components used in packages of food and beverages. An obsesogenic and diabetogenic substance is the bisphenol A (BPA), used in manufacture of polycarbonate plastic and epoxy resin. Our exposure to this substance may begin during fetal development and in the first hours of life still in hospital. The aim of this study was to investigate the effects of BPA in islets from newborn mice. Neonate pancreatic islets (4-6 days) were isolate by collagenase method and were cultured with BPA (0.1 nM) for 48 hours, and then used to evaluate: 1) insulin secretion; 2) gene expression; 3) protein content. The results were analyzed by Student t-test, p<0.05. We observed a reduced insulin secretion in response to both glucose and 40 mM KCl solution. However, total insulin content and Ins1/Ins2 gene expression was not altered. On the other hand, connexin 36 gene and protein expression were decreased. Another genes involved with b-cell maturation were unchanged. Furthermore, BPA decreased gene expression of beta 2 subunit of L-type calcium channel. Protein content of K-ATP channel (kir6.2 and sur1), vamp2 and syntaxin 1A were also reduced. We concluded that 0.1 nM BPA exposure for 48 h alters molecular mechanisms involved with insulin secretion from newborn islets in culture / Mestrado / Fisiologia / Mestra em Biologia Funcional e Molecular

Orientador: Sebastião Roberto Taboga / Coorientador: Silvana Gisele Pegorin de Campos / Banca: Ana Claudia Polli Lopes / Banca: Ana Paula Girol / Banca: Maria Tercilia Vilela de Azeredo Oliveira / Banca: Claudia Regina Bonini Domingos / Resumo: A incidência de câncer de mama tem aumentado consideravelmente ao longo dos anos. Frente a esta alta taxa epidemiológica a atenção às causas desta doença tem sido significativa em meio a grupos de pesquisa. Fatores genéticos e algumas situações de risco, como a exposição a componentes químicos disruptores endócrinos, podem estimular o seu desenvolvimento. O bisfenol A (BPA), utilizado na manufatura de plásticos e resinas, pode ser liberado destes componentes e exercer efeitos estrogênicos, causando distúrbios na função endócrina e aumentando a predisposição à carcinogênese. Alguns estudos têm demonstrado os efeitos do BPA em longo prazo, de modo que sua exposição durante o período de desenvolvimento embrionário inicial e perinatal pode predispor a glândula mamária (GM) ao desenvolvimento de câncer em indivíduos já adultos. Seu mecanismo de ação, assim como o do estradiol endógeno, baseia-se principalmente na ligação a receptores celulares hormonais, podendo estimular a proliferação, promovendo um desbalanço nos ciclos de renovação celular mamária. Para o estudo de carcinogênese o gerbilo da Mongólia (Meriones unguiculatus) é um modelo experimental interessante, já que possui capacidade de desenvolver tumores espontâneos em órgãos hormônio-responsivos, mimetizando, naturalmente, o ambiente de um indivíduo predisposto à tumorigênese. Assim, os objetivos deste trabalho foram (1) caracterizar morfologicamente a GM de fêmeas de gerbilo da Mongólia em diferentes estágios... / Abstract: The incidence of breast cancer has increased considerably over the years. Facing this high epidemiological rate, attention to the causes of this disease has been significant among research groups. Genetic factors and some risk situations, such as exposure to chemical endocrine disrupting components may stimulate its development. Bisphenol A (BPA), a compound used in the manufacture of plastics and resins, can be released from these components and exert estrogenic effects, causing disturbances of endocrine function and increasing the predisposition to carcinogenesis. Some studies have demonstrated the long-term effects of BPA, in a way that exposure during embryonic development (perinatal phase) may predispose the mammary gland (MG) to development of cancer in adults. Its mechanism of action, as that of endogenous estradiol, is mainly based on cellular hormonal receptors binding, which can stimulate the proliferation, promoting an imbalance of breast cell cycles and renewal. For these carcinogenesis studies, the Mongolian gerbil (Meriones unguiculatus) is an interesting experimental model, since it has the ability to develop spontaneous tumors in hormone-responsive organs, naturally mimicking the environment of an individual predisposed to tumorigenesis. Thus, the aims of this study were to (1) characterize morphologically the mammary gland of Mongolian gerbil females at different stages of functionality, (2) describe morphological changes found in the MG of adult females ... / Doutor

Endocrine disrupting chemicals (EDCs) are ubiquitous in the environment and have been detected in drinking water. Although various water treatment processes can remove EDCs, chemicals can migrate from pipes that transport water and contaminate drinking water. Globally bottled water consumption is steadily rising as an alternative to tap water, but EDCs have also been detected in bottled water. Sources of EDCs in bottled water include contamination of the water source, contamination through the production process or the migration of EDCs from the packaging material. There is limited information on EDCs in drinking water and bottled water from South Africa. The aim of this study was to determine the estrogenic activity, levels of selected EDCs and the potential health risks associated with the consumption of water from selected distribution points in Pretoria (City of Tshwane) and Cape Town as well as bottled water. The study consisted of 3 phases. Phase 1 included the analysis of drinking water samples from ten water distribution points in Pretoria and Cape Town collected over four sampling periods. In phase 2, ten brands of bottled water were analysed after exposure to different storage conditions (20°C, 40°C, light and dark) for 10 days. Samples were extracted using a C18 solid phase extraction method. Estrogenic activity was assessed using the recombinant yeast estrogen screen (YES) bioassay and the T47D-KBluc reporter gene bioassay. The extracts were analysed for di(2-ethylhexyl) adipate (DEHA), di(2-ethylhexyl) phthalate (DEHP), diisononylphthalate (DINP), dibutyl phthalate (DBP), bisphenol A (BPA), nonylphenol (NP), 17β-estradiol (E2), estrone (E1) and ethynylestradiol (EE2) using UPLC-MS. Phase 3 consisted of a scenario based health risk assessment to assess the carcinogenic and toxic human health risks associated with the consumption of distribution point and bottled water. All the samples were below the detection limit (dl) in the YES bioassay, but estrogenic activity was detected in bottled and distribution point water using the T47D-KBluc bioassay. All samples were below the 0.7 ng/L trigger value for estrogenic activity in drinking water. NP was below the dl for all the samples, E2 was detected in five distribution point samples and E1, EE2, DEHA, DEHP, DINP, DBP and BPA were detected in distribution point and bottled water samples. The estrogenic activity and levels of target chemicals were comparable to the levels found in other countries. Hazard quotients for BPA, DEHA and DINP were higher in bottled water compared to distribution point water. The greatest non-carcinogenic health risk was posed by E1 in distribution point water from Pretoria and the highest cancer risk by levels of DEHP in distribution point water from Cape Town. However, overall, health risk assessment revealed acceptable health and carcinogenic risks associated with the consumption of distribution point and bottled water. Although the potential health risks posed by the EDCs found in the water samples in this study were low, the fact that potential EDCs were found in the water samples are still of concern. A monitoring strategy that also includes water from other municipalities and other brands of bottled water are therefore recommended. / Thesis (PhD)--University of Pretoria, 2016. / School of Health Systems and Public Health (SHSPH) / PhD / Unrestricted

Orientador: Sebastião Roberto Taboga / Resumo: A próstata é uma glândula componente do sistema genital dos mamíferos e sua principal função prostática é secretar um fluido levemente alcalino (pH 7,29) que contribui para a formação do líquido seminal. As fêmeas em certas espécies, como o roedor gerbilo da Mongólia (Meriones unguiculatus), apresentam próstata cuja morfologia se assemelha à porção ventral do complexo prostático masculino e à próstata feminina em humanos. Nas últimas décadas tem sido relatado um constante aumento da exposição a substâncias capazes de interferir na ação hormonal, conhecidas como disruptores endócrinos. O bisfenol A (BPA) pertence a uma das categorias de disruptores endócrinos presentes no meio ambiente. Estudos demonstram que a exposição a esse composto interfere negativamente na morfofisiologia prostática, favorecendo o estabelecimento de lesões pré-malignas e malignas. Além do BPA, uma das constantes problemáticas dos dias atuais é a exposição ambiental a hormônios exógenos como o estradiol (E2). Desta forma, a administração de fármacos com estrutura semelhante a hormônios esteroides pode exercer efeitos sobre a glândula, uma vez que os mesmos se ligam a seus receptores hormonais afetando a homeostasia prostática. O presente estudo teve como objetivo verificar as alterações morfofuncionais na próstata de fêmeas de gerbilo da Mongólia após tratamento perinatal com dose diária ambiental, ou seja, dose ambiental segura de BPA (50 µg/kg) e doses de 17-β estradiol (35 µg/kg), 3 vezes por semana p... (Resumo completo, clicar acesso eletrônico abaixo) / Mestre

A designed series of directly copolymerized homo- and disulfonated copolymers containing controlled degrees of pendant sulfonic acid groups have been synthesized via nucleophilic step polymerization. Novel sulfonated poly (arylene ether sulfone) copolymers using 4,4'-bisphenol A, 4,4'-biphenol, hexafluorinated (6F) bisphenol AF, and hydroquinone, respectively, with dichlorodiphenyl sulfone (DCDPS) and 3,3'-disodiumsulfonyl-4,4'-dichlorodiphenylsulfone (SDCDPS) were investigated. Molar ratios of DCDPS and SDCDPS were systematically varied to produce copolymers of controlled compositions, which contained up to 70 mol% of disulfonic acid moiety. The goal is to identify thermally, hydrolytically, and oxidatively stable high molecular weight, film-forming, ductile ion conducting copolymers, which had properties desirable for proton exchange membranes (PEM) in fuel cells. Commercially available bisphenols were selected to produce cost effective alternative PEMs. Partially aliphatic bisphenol A and hexafluorinated (6F) bisphenol AF produced amorphous copolymers with different thermal oxidative and surface properties. Biphenol and hydroquinone was utilized to produce wholly aromatic copolymers. The sulfonated copolymers were prepared in the sodium-salt form and converted to the acid moiety via two different methodologies and subsequently investigated as proton exchange membranes for fuel cells. Hydrophilicity increased with the level of disulfonation, as expected. Moreover, water sorption increased with increasing mole percent incorporation of SDCDPS. The copolymers' water uptake was a function of both bisphenol structure and degree of disulfonation. Furthermore, the acidification procedures were shown to influence the Tg values, water uptake, and conductivity of the copolymers. Atomic force microscopy (AFM) in the tapping mode confirmed that the morphology of the copolymers could be designed to display nanophase separation in the hydrophobic and hydrophilic (sulfonated) regions. Morphology with either co-continuous hydrophobic or hydrophilic domains could be attained for all the sulfonated copolymers. The degree of disulfonation required for continuity of the hydrophilic phase varied with biphenol structure. Proton conductivity values for the sulfonated copolymers, under fully hydrated conditions, were a function of bisphenol and degree of sulfonation. However, at equivalent ion exchange capacities the proton conductivities were comparable. A careful balance of copolymer composition and acidification method was necessary to afford a morphology that produced ductile films, which were also sufficiently proton conductive. The copolymers of optimum design produced values of 0.1 S/cm or higher, which were comparable to the commercial polyperfluorosulfonic acid material Nafion™ control. / Ph. D.

La thèse s'intéresse à la présence et au devenir de sept alkylphénols et du bisphénol A (BPA) dans un bassin versant dont une partie est très urbanisée et l'autre fait l'objet d'une exploitation agricole intense : le bassin de la Seine, dans sa zone centrale (région Île-de-France). Elle est organisée autour de quatre approches. Dans une première approche les sources urbaines ont été caractérisées. Pour cela, les rejets des 5 plus grandes stations d'épuration (STEP) de la région Île-de-France (IDF), les rejets urbains de temps de pluie (RUTP), les eaux de ruissellement urbain en réseaux séparatifs et les retombées atmosphériques ont été analysés. Cette étude a révélé que le BPA était majoritairement présent dans les sources de temps de pluie (RUTP + eau de ruissellement) tandis que l'acide nonylphénoxy acétique (NP1EC), un précurseur du 4-nonylphénol (4-NP), est dominant dans les rejets de STEP. Le 4-NP a, lui, été retrouvé dans toutes les sources étudiées à des concentrations avoisinant la centaine de nanogrammes par litre (ng.l-1), témoignant de sa forte dissémination dans l'environnement urbain. Dans un second temps, l'imprégnation du milieu a été considérée au niveau des eaux de surface et des sols, à deux échelles d'observation. La première échelle est le bassin de l'Orgeval, caractéristique d'un petit bassin amont, tandis que la seconde échelle intègre l'ensemble de la région IDF et l'agglomération parisienne. Ces deux échelles ont permis de mettre en évidence une dissémination importante du 4-NP à l'ensemble des matrices naturelles du bassin de la Seine. A l'échelle de l'IDF, l'influence de l'agglomération parisienne a été démontrée sur les concentrations de NP1EC et BPA dans la Seine. Puis, la biodégradabilité des composés nonylphénoliques dans la Seine a été déterminée par une approche innovante. Les constantes de biodégradabilité ont été déterminées directement dans la Seine à l'aide du modèle ProSe (développé par le Centre de Géosciences, Ecole des Mines ParisTech) et de campagnes de prélèvement spécifiques sur le fleuve (suivi d'une masse d'eau). Les constantes de biodégradation simulées dans la Seine présentent de très fortes variabilités en fonction des conditions hydrauliques et climatiques. Après un épisode de bloom algal, les constantes de biodégradation des composés nonylphénoliques se sont avérées être 10 à 35 fois supérieures à celles retrouvées en conditions classiquement rencontrées en Seine. Enfin, les flux d'alkylphénols et de BPA exportés par la Seine ont été comparés aux flux émis par les sources urbaines au niveau annuel. A l'échelle de l'année (2010), les flux de 4-NP et de BPA émis par l'ensemble des sources urbaines considérées ne sont pas prédominants devant les flux exportés par la Seine à l'aval de l'agglomération parisienne. Ce résultat vient une fois de plus confirmer la dissémination importante du 4-NP et du BPA dans toute la région IDF en raison de leur forte utilisation depuis les années 1960. Il soulève également plusieurs questions concernant les sources actuelles des flux retrouvés et la contamination des zones amont du bassin de la Seine. Cette thèse a été effectuée dans le cadre des programmes PIREN-Seine et OPUR (Observatoire des Polluants URbains) / This thesis focuses on occurrence and fate of seven alkylphenols and bisphenol A (BPA) on a basin divided into a heavily urbanized part and a second part which underscore intense agricultural activities : the Seine River basin (Île-de-France Region). This study was divided into four different approaches. The first approach consists in studying the contamination of urban sources. To this end, the effluents of the five biggest wastewater treatment plants (WWTP) of the IDF Region, combined sewer overflows (CSO), urban runoff and total atmospheric fallouts were considered. This study highlight that BPA mainly occurs in wet-weather urban sources (CSO and urban runoff) while WWTP effluents are dominated by the nonylphenoxy acetic acid (NP1EC) which is a 4 nonylphenol (4 NP) precursor. The 4-NP was found in all investigated urban sources at level close to a hundred of nanogram per liter (ng.l-1). The second approach focuses on the assessment of contamination of natural matrices such as receiving surface water and soils at different scales. The first scale is the study of the Orgeval River basin which is representative of basins unpolluted by urban activities, while the second scale accounts the entire IDF region including the Parisian Metropolitan area. These two scales revealed the large spread of 4-NP to all investigated natural matrices within the Seine River basin. At the scale of the IDF Region, the influence of the Parisian Metropolitan Area was demonstrated on NP1EC and BPA concentrations within the Seine River. On a third step, the biodegradability of nonylphenolic compounds was investigated according to an innovative approach. The biodegradation rates were determined directly within the Seine River according to the ProSe model (Centre de Géoscience, école des Mines ParisTech) and specific sampling campaigns performed on the Seine River. The biodegradation rates found during this study disclosed high variabilities according to biological conditions of the Seine River. Actually, after an algal bloom, the biodegradation rates were found between 10 and 35 times higher than those established under common biological conditions. At last, the fluxes exported by the Seine River, at annually scale, were compared to those emitted by all investigated urban sources. At the scale of year 2010, fluxes of 4-NP and BPA emitted by all investigated urban sources are not predominant compared with those exported by the Seine River at the outlet of the Parisian Metropolitan Area. This result confirms the large spread of 4-NP and BPA at the scale of the entire IDF Region likely due to their important uses since the 1960's. This result also raises some questions about the origins of such fluxes found in Seine River and about the contamination of the upstream part.This thesis was performed within the framework of the PIREN-Seine and OPUR (Observatoire des Polluants URbains) research programs

Thousands of synthetic chemicals have been released into the environment, causing widespread exposures of wildlife and humans alike. Some of these chemicals are known to disrupt aspects of hormone action thus inducing abnormalities in endocrine tissues and organs. Bisphenol S (BPS) and tetrabromobisphenol A (TBBPA), two largely unstudied chemicals commonly used in consumer products, are suspected to have endocrine disrupting properties based on their similar chemical structures to known endocrine disrupting chemicals (EDCs). To determine whether developmental exposure to BPS or TBBPA induced abnormalities in the ovary, mice were administered oil, BPS or TBBPA during pregnancy and lactation. The ovaries of female offspring were examined for gross morphological, immunohistological and gene expression differences at postnatal day (PND) 22 and week 16. To determine whether these exposures alter responses to hormones, two females from each litter were administered either oil or ethinyl estradiol (EE2) from PND 19-21. Our study identified significant differences in ovarian follicular formation and gene expression after developmental TBBPA and BPS exposures. Most effects were observed at PND22 (pre-puberty), and were apparent after the EE2 challenge, suggesting that changes induced by BPS and TBBPA are age- and hormone- dependent. Our results are consistent with the hypothesis that TBBPA and BPS are EDCs; that these compounds can disrupt development of the ovary; and that the observed effects of TBBPA and BPS exposure are similar to risk factors for ovarian diseases including cancer. These findings may indicate that widespread exposures to BPS and TBBPA could have implications for public health.