Este trabalho teve como objetivo investigar os efeitos da exposição pré-natal a duas doses de etanol sobre o desenvolvimento e a atenção de ratos. Método: 49 ratas Wistar prenhes distribuídas em quatro grupos de acordo com o tratamento gestacional: A35 – dieta líquida com 35% de calorias derivadas do etanol (CDE): A10 – dieta líquida com 10% CDE; Controle – dieta líquida sem etanol; Chow – livre acesso à água e ração. No estudo I, foram avaliados o peso, os reflexos (geotaxia negativa e força de agarrar) e a atividade locomotora dos filhotes. No grupo A35, apenas 43% dos filhotes sobreviveram. Os animais desse grupo apresentaram menor peso que os demais, prejuízos na tarefa de força de agarrar e maior atividade locomotora. No estudo II, 12 filhotes machos adultos de cada grupo foram testados na Tarefa serial de cinco escolhas. Os animais do grupo A35 apresentaram maior número de omissões, principalmente no final das sessões. Conclusão: Efeitos do etanol são dose-dependentes e podem estar associados com um prejuízo atencional específico. / The objective of this study was to investigate the effects of prenatal exposure to two doses of ethanol on developmental milestones and attention of rats. Method: 49 pregnant Wistar rats were assigned to one of four gestational treatments: A35 - liquid diet with 35% ethanol-derived calories (EDC); A10 - liquid diet with 10% EDC; Control – ethanol-free liquid diet; Chow – laboratory chow and water. In study I, litters were tested for body weight, negative geotaxis, grip strength and locomotor activity. Only 43% of A35 pups survived. A35 weighed less than other groups, performed worse in grip strength and presented more locomotor activity. In study II, 12 male twomonth old rats from each group were tested in the Five choice serial reaction time task. A35 performed more omission errors than other groups, mainly during the final part of the sessions. Conclusion: Ethanol effects are dose-dependent and might be associated with a specific attentional deficit.

Este trabalho teve como objetivo investigar os efeitos da exposição pré-natal a duas doses de etanol sobre o desenvolvimento e a atenção de ratos. Método: 49 ratas Wistar prenhes distribuídas em quatro grupos de acordo com o tratamento gestacional: A35 – dieta líquida com 35% de calorias derivadas do etanol (CDE): A10 – dieta líquida com 10% CDE; Controle – dieta líquida sem etanol; Chow – livre acesso à água e ração. No estudo I, foram avaliados o peso, os reflexos (geotaxia negativa e força de agarrar) e a atividade locomotora dos filhotes. No grupo A35, apenas 43% dos filhotes sobreviveram. Os animais desse grupo apresentaram menor peso que os demais, prejuízos na tarefa de força de agarrar e maior atividade locomotora. No estudo II, 12 filhotes machos adultos de cada grupo foram testados na Tarefa serial de cinco escolhas. Os animais do grupo A35 apresentaram maior número de omissões, principalmente no final das sessões. Conclusão: Efeitos do etanol são dose-dependentes e podem estar associados com um prejuízo atencional específico. / The objective of this study was to investigate the effects of prenatal exposure to two doses of ethanol on developmental milestones and attention of rats. Method: 49 pregnant Wistar rats were assigned to one of four gestational treatments: A35 - liquid diet with 35% ethanol-derived calories (EDC); A10 - liquid diet with 10% EDC; Control – ethanol-free liquid diet; Chow – laboratory chow and water. In study I, litters were tested for body weight, negative geotaxis, grip strength and locomotor activity. Only 43% of A35 pups survived. A35 weighed less than other groups, performed worse in grip strength and presented more locomotor activity. In study II, 12 male twomonth old rats from each group were tested in the Five choice serial reaction time task. A35 performed more omission errors than other groups, mainly during the final part of the sessions. Conclusion: Ethanol effects are dose-dependent and might be associated with a specific attentional deficit.

Diversos estudos observaram uma correlação entre doenças na idade adulta e o ambiente durante a vida fetal. O estudo realizado por Barker e colaboradores foi um dos primeiros a relatar a hipótese de um possível envolvimento do ambiente intra-uterino com o desenvolvimento de doenças cardiovasculares, mas os mecanismos responsáveis por esta associação ainda não são totalmente conhecidos. Estudos demonstraram uma associação entre baixo peso ao nascimento com resistência à insulina e intolerância à glicose na vida adulta. Recentemente, verificamos que o consumo de dieta hipossódica, conhecido modelo de resistência à insulina, durante a gestação e lactação está vinculado a menor sensibilidade à insulina na prole adulta. Visto que a presença de resistência à insulina durante a gestação leva a diversas alterações metabólicas na prole adulta, pode-se supor que a sobrecarga de sacarose, um modelo de resistência à insulina, durante a gestação e lactação influencie no desenvolvimento da prole. Assim, o objetivo do presente estudo foi verificar a repercussão da resistência à insulina, durante a gestação sobre a prole adulta. Para tanto, ratas Wistar foram alimentadas com dieta hipo (HO) ou normossódica (NR) suplementadas ou não com sacarose (NR+SAC - 20g/dL) ou maltodextrina (NR+MALTO - 20g/dL) desde a oitava semana de vida até o final da gestação e amamentação. Na prole resultante destes animais foi observado menor peso ao nascimento nos grupos HO, NR+SAC e NR+MALTO. Esta alteração resultou no desenvolvimento de maior insulinemia, pressão arterial e maior captação de glicose na prole de fêmeas das mães do grupo NR+SAC. Os machos apresentaram menor índice de adiposidade e maior expressão gênica renal dos componentes do sistema renina-angiotensina. Tais resultados nos permitem concluir que a sobrecarga de carboidratos durante a gestação e lactação está associada a alterações no peso ao nascimento e no metabolismo da insulina na idade adulta. É possível que a ativação do sistema renina-angiotensina materno induzido pela sobrecarga de carboidrato esteja associada a alterações deste mesmo sistema observado na prole adulta. / Many studies observed a correlation between diseases in adult subjects and the environment during the fetal life. Barker and coworkers hypothesized that there is a possible intrauterine enviroment association with cardiovascular diseases in adulthood. The mechanisms responsible for this association are still not very well known. Recently, we have verified that low-salt diet consumption, a well-known model of insulin resistance, during pregnancy and lactation is associated with a lower insulin sensitivity in the adult offspring. Since insulin resistance during pregnancy leads to many metabolic alterations in the adult offspring, we suppose that sucrose overload during pregnancy and lactation could influence the offspring development. The aim of this study was to verify the effects on adult offspring of insulin resistance during pregnancy and lactation. Female Wistar rats were fed low (LSD) and normal-salt diet (NSD) supplemented or not with sucrose (SUC - 20 g/dL) or maltodextrin (MALTO - 20 g/dL) until the end of pregnancy and lactation. Lower birth weight was observed in offspring of LSD, SUC and MALTO groups. Higher plasma insulin level, blood pressure and glucose uptake was detected in the adult SUC female offspring. SUC male offspring had lower adiposity index and higher gene expression of the renal renin-angiotensin components. These results show that carbohydrate overload during pregnancy and lactation is associated with alterations in birth weight and in insulin metabolism at adult life. It is possible that the maternal renin-angiotensin system activation by the carbohydrate overload is associated with alterations in the same system observed in the adult offspring.

Magister Psychologiae - MPsych / The study made use of cross-sectional design that compared the performance of younger children (6- to 7-year-olds) with that of older children (12- to 13-year-olds) on various measures of executive function. Within this, it made use of a natural experimental design, with children exposed to alcohol as the experimental group and non-exposed children as the control group.

Les tumeurs germinales du testicule (TGT) représentent le cancer le plus fréquent chez les hommes Européens âgés de 15 et 39 ans. L'incidence a doublé dans la plupart des pays Européens depuis 30 ans. Cette augmentation rapide, les variations géographiques d'incidence et les études chez les populations migrantes suggèrent un rôle des facteurs environnementaux dans le développement des TGT. Cette thèse propose de contribuer à l'amélioration des connaissances concernant l'évolution du TGT en clarifiant l'impact des expositions environnementales et professionnelles, notamment pendant la période prénatale. Les objectifs principaux sont de: 1. Prédire l'incidence du TGT jusqu'en 2025 en estimant la part d'augmentation due aux changements démographiques afin d'obtenir une estimation de l'augmentation due aux risques. 2. Faire un bilan de l'état des connaissances sur l'association entre les expositions environnementales et professionnelles et le développement du TGT dans une revue systématique de littérature 3. Investiguer l'association entre l'exposition parentale professionnelle aux pesticides en période prénatale et le TGT parmi la descendance Les résultats montrent que l'incidence du TGT continue d'augmenter, mettant en avant un fort impact environnemental dans l'évolution du TGT. Néanmoins, la revue de littérature ne permettait pas d'identifier de facteurs de risque environnementaux avérés, mais montrait un manque d'études investiguant les expositions prénatales sur le risque de TGT. L'étude NORD-TEST menée sur les données de registre de quatre pays nordiques est l'étude la plus puissante à ce jour et ne montre aucune association entre l'exposition parentale professionnelle aux pesticides en période prénatale et le TGT / Testicular germ cell tumours (TGCT) are the most common cancer diagnosed among young European men aged between 15 and 39 years. TGCT incidence rates have doubled in most European countries over the last 30 years. This rapid increase in incidence, the geographical variations and the studies in migrant populations suggest a role of environmental factors in TGCT aetiology. This thesis aims to contribute to the knowledge of TGCT evolution by studying the impact of environmental and occupational exposures, especially during the prenatal period. The objectives are: 1. To estimate the proportion of the increased incidence due to overall changes in risk patterns compared to the proportion due to demographic changes, by predicting the future testicular cancer trends in Europe 2. To summarize and evaluate the current knowledge on environmental and occupational exposures related to TGCT risk by means of a systematic literature review 3. To investigate the association between the prenatal parental occupational exposure to pesticides and TGCT risk in the offspring. The results show that the TGCT incidence continues to increase, supporting an environmental impact on TGCT evolution. From the epidemiological literature to date no specific environmental risk factors emerge; however, there have clearly been a lack of studies investigating prenatal exposures on TGCT risk. The NORD-TEST study, based on registry data from four Nordic countries, is the largest study to date. No association was found between parental occupational exposure to pesticides during prenatal period and TGCT risk

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Contexte : L’organisme en développement est très sensible à son environnement. Plusieurs études épidémiologiques ont suggéré la toxicité développementale d’une dizaine de polluants suite à des expositions prénatales. L’objectif général de cette thèse est d’évaluer les conséquences des expositions à des polluants chimiques (consommation de produits de la mer comme vecteur de contamination, solvants organiques et insecticides organophosphorés) pendant la grossesse sur le développement de l’enfant à 2 ans en se focalisant sur le développement neuro-comportemental, le développement respiratoire et immunitaire et le développement staturo-pondéral. Matériel et méthodes : Ce travail s’est appuyé sur la cohorte mère-enfant PELAGIE, mise en place en Bretagne entre 2002 et 2006. Près de 3500 femmes ont été incluses en début de grossesse et environ 1500 couples mère-enfant ont été suivis à 2 ans. Les expositions ont été évaluées en début de grossesse à partir de questionnaires, de matrices emplois-expositions ou de dosage de biomarqueurs d’exposition. Les indicateurs de santé ont été mesurés lors du suivi à 2 ans par questionnaire permettant de recueillir des éléments sur le comportement, les manifestations respiratoires à type de sifflement, les maladies allergiques et la croissance entre la naissance et 2 ans. Résultats : L’exposition professionnelle prénatale aux solvants organiques était associée à des déficits de l’attention/hyperactivité et des niveaux d’agressivité plus importants chez l’enfant à 2 ans. Cette exposition n’était pas associée avec les manifestations respiratoires et allergiques. Nous avons aussi montré que la consommation maternelle de coquillages et crustacés pendant la grossesse était associée à une augmentation du risque d’allergie alimentaire chez l’enfant. Enfin, l’exposition prénatale aux insecticides organophosphorés a été associée à une diminution de la vitesse de croissance en taille à 2 ans. Conclusion : Ce travail renforce l’hypothèse de l’implication de l’exposition prénatale aux polluants chimiques de l’environnement, y compris à faible dose, dans l’origine développementale de la santé et des maladies. / Background: The organism is very sensitive to environment during its developmental period. Number of epidemiological studies has suggested the developmental toxicity of about ten chemical pollutants after prenatal exposure. The general objective of the thesis is to explore the effect of prenatal exposure to certain chemical pollutants (organic solvents, organophosphates pesticides and maternal consumption of fish and shellfish (vectors of pollutants)) on child development at age 2. Methods: This thesis is based on the PELAGIE mother-child cohort that was set up in 2002, in Brittany (FRANCE). In total, 3421 women were included in this cohort at the beginning of pregnancy and 1500 mother- child pairs were followed when the child was 2 years old. Exposures were evaluated at the beginning of pregnancy from questionnaires, job-exposure matrices or measurement of biomarkers of exposure. Health indicators were measured at the 2 years follow-up. At follow-up, questionnaires allowed to obtain information on child behaviour, respiratory manifestations like wheezing, allergies (eczema and food allergy) and growth between birth and the age of two. Results: Prenatal occupational exposure to solvents was associated with higher level of hyperactivity and attention deficit at age 2. This exposure was not associated neither with respiratory nor with allergic manifestations. We also observed that maternal shellfish consumption during pregnancy was associated with a higher risk of food allergy in preschoolers. Finally, higher prenatal exposure to organophosphate pesticides was associated with a decrease height growth velocity at age 2. Conclusion: The present thesis based on the PELAGIE study supported for the hypothesis that prenatal exposure to environmental chemicals may be implicated in the developmental origin of health and diseases.

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