p. 1-86 / Submitted by Santiago Fabio (fabio.ssantiago@hotmail.com) on 2013-04-09T19:38:13Z No. of bitstreams: 1 Dissertacao Tchana de Oliveira.pdf: 985133 bytes, checksum: 73cb03cf5f89412625c24bc2f8722bed (MD5) / Approved for entry into archive by Rodrigo Meirelles(rodrigomei@ufba.br) on 2013-04-10T14:05:18Z (GMT) No. of bitstreams: 1 Dissertacao Tchana de Oliveira.pdf: 985133 bytes, checksum: 73cb03cf5f89412625c24bc2f8722bed (MD5) / Made available in DSpace on 2013-04-10T14:05:18Z (GMT). No. of bitstreams: 1 Dissertacao Tchana de Oliveira.pdf: 985133 bytes, checksum: 73cb03cf5f89412625c24bc2f8722bed (MD5) Previous issue date: 2010 / A gestação e lactação são períodos caracterizados pelo desenvolvimento e modulação dos sistemas orgânicos. A dieta materna durante este período crítico do desenvolvimento exerce um importante papel na regulação da homeostase dos descendentes e pode trazer conseqüências até a vida adulta. Assim, o presente estudo teve como objetivo investigar os efeitos de uma dieta hiperlipídica durante a gestação e lactação sobre a evolução ponderal, o perfil lipídico, a glicemia, os produtos nitrogenados não protéicos e o consumo alimentar dos descendentes na vida adulta. Fêmeas de ratos Wistar foram alimentadas com dieta hiperlipídica ou dieta padrão durante a gestação e lactação. Os descendentes foram divididos em dois grupos: Descendente Controle (DC, n=10) descendentes de ratas alimentadas com dieta padrão e Descendente Hiperlipídica (DH, n=10) descendentes de ratas alimentadas com a dieta hiperlipídica. Após o desmame ambos os grupos foram alimentados com dieta padrão até a vida adulta. O grupo DH apresentou aumento (p≤0,05), no perfil lipídico, na glicemia e no consumo quando comparado ao grupo controle. Os resultados sugerem que a exposição no período perinatal a dieta hiperlipídica, rica em ácidos graxos saturados pode programar alterações no metabolismo dos descendentes adultos mesmo quando expostos a dieta nutricionalmente equilibrada ao longo da vida. / Salvador

Conselho Nacional de Desenvolvimento Científico e Tecnológico / O consumo materno de dieta hiperlipídica saturada durante a gestação e lactação favorece o desenvolvimento obesidade e anormalidades metabólicas na prole. Este trabalho teve como objetivo testar a hipótese de que a prole proveniente de mães alimentadas com dieta hiperlipídica durante a gestação e lactação desenvolve obesidade e anormalidades metabólicas e de que essas alterações estão associadas a resistência central a leptina. As ratas grávidas da linhagem C57BL/6 (n=20) foram alimentadas com dieta standard chow (SC; 19% de lipídeos) ou dieta hiperlipídica (HF; 49% de lipídeos) durante todo período de gestação e lactação. Após o desmame, a prole de machos foi dividida em quatro grupos experimentais, de acordo com a dieta das mães e da prole: SC(mães)/SC(prole), SC/HF, HF/SC e HF/HF (n=12/gp). As características metabólicas foram avaliadas pela curva de ganho de peso; medida da pressão arterial; glicose de jejum, área sob a curva no teste oral de tolerância a glicose; concentrações de triglicerídeos hepáticos e estimativa da esteatose hepática; análise plasmática de insulina e leptina e; distribuição e análise morfológica do tecido adiposo. Para analisar a sensibilidade a leptina, os quatro grupos originais foram subdivididos em dois grupos cada (veículo ou leptina-5g) para verificar a resposta alimentar (g) após o tratamento agudo intracerebroventricular (ICV) e a sinalização hipotalâmica de leptina. A dieta HF durante o período pós-desmame (grupo SC/HF), durante gestação e lactação (grupo HF/SC), ou ambos os períodos (grupo HF/HF), promoveu aumento da massa corporal. No que concerne as alterações hepáticas e a ação da insulina, a dieta HF durante o período perinatal favoreceu 25% de esteatose hepática, hiperinsulinemia e hiperleptinemia, enquanto os demais grupos experimentais SC/HF e HF/HF, demonstraram um padrão mais exacerbado. A avaliação da distribuição e morfometria do tecido adiposo demonstra o importante papel da dieta HF perinatal em amplificar a habilidade de estocar gordura visceral na prole. Considerando a ação central da leptina nos grupos tratados, a resposta alimentar mostrou-se atenuada em SC/HF, indicando o efeito determinante da dieta pós-desmame sobre a ação da leptina nesse modelo. Os resultados indicam fortemente que a dieta HF materna afeta a saúde da prole adulta. Especificamente, a prole programada apresenta esteatose hepática, hipertrofia de adipócitos, aumento de gordura visceral, hiperleptinemia e resistência a insulina. Esse fenótipo não está associado a resistência central a leptina na prole aos três meses de idade. / Maternal high-fat diet consumption during pregnancy and lactation causes metabolic abnormalities (MA) (similar to metabolic syndrome in humans) in the rodents offspring. We tested the hypothesis that the offspring of dams fed a high fat diet during pregnancy and lactation develop MA and leptin resistance.Pregnant C57BL6 mice (n=20) were fed either standard chow (SC; 19% fat) or a high fat diet (HF; 49% fat). After weaning, male offspring were divided into four groups according to the diet of dams and offspring: SC(dams)/SC(offspring), SC/HF, HF/SC and HF/HF (n=12/group). MA were characterized by weight gain curve measured weekly; tail-cuff systolic pressure; fast glucose and areas under the curve after oral glucose tolerance test; fat mass depots; leptin and insulin concentrations, all performed at 12 weeks of age.To analyze leptin sensitivity, each group was divided into two groups (vehicle or leptin-5g) to identify the feeding response and pSTAT3 expression after acute intracerebroventricular (ICV) treatment (n=6/group). The HF schedule during post-weaning (SC/HF group), during gestation and lactation (HF/SC group), or both periods (HF/HF group), increased body mass in experimental groups. In respect to hepatic alterations and insulin action, the HF diet during gestation and lactation caused 25% of liver steatosis, hiperinsulinemia and hiperleptinemia, whereas SC/HF and HF/HF presented worst patterns. The fat distribution and morphometry pointed for the key role of HF during gestation and lactation in amplify the ability to store fat in the offspring. Considering the central leptin action in offspring treated groups, SC/HF was not responsive to leptin treatment, which strong indicates the determining effect of post-weaning diet upon leptin action in this model. The compelling results indicate that maternal HF schedule during pregnancy and lactation affects the offpring health. Specifically, programmed offspring presented liver steatosis, adipocyte hipertrophy, increased visceral fat, hiperleptinemia and insulin resistance. This phenotype was not associated with central leptin resistance in offspring at 3 month-age.

Conselho Nacional de Desenvolvimento Científico e Tecnológico / O consumo materno de dieta hiperlipídica saturada durante a gestação e lactação favorece o desenvolvimento obesidade e anormalidades metabólicas na prole. Este trabalho teve como objetivo testar a hipótese de que a prole proveniente de mães alimentadas com dieta hiperlipídica durante a gestação e lactação desenvolve obesidade e anormalidades metabólicas e de que essas alterações estão associadas a resistência central a leptina. As ratas grávidas da linhagem C57BL/6 (n=20) foram alimentadas com dieta standard chow (SC; 19% de lipídeos) ou dieta hiperlipídica (HF; 49% de lipídeos) durante todo período de gestação e lactação. Após o desmame, a prole de machos foi dividida em quatro grupos experimentais, de acordo com a dieta das mães e da prole: SC(mães)/SC(prole), SC/HF, HF/SC e HF/HF (n=12/gp). As características metabólicas foram avaliadas pela curva de ganho de peso; medida da pressão arterial; glicose de jejum, área sob a curva no teste oral de tolerância a glicose; concentrações de triglicerídeos hepáticos e estimativa da esteatose hepática; análise plasmática de insulina e leptina e; distribuição e análise morfológica do tecido adiposo. Para analisar a sensibilidade a leptina, os quatro grupos originais foram subdivididos em dois grupos cada (veículo ou leptina-5g) para verificar a resposta alimentar (g) após o tratamento agudo intracerebroventricular (ICV) e a sinalização hipotalâmica de leptina. A dieta HF durante o período pós-desmame (grupo SC/HF), durante gestação e lactação (grupo HF/SC), ou ambos os períodos (grupo HF/HF), promoveu aumento da massa corporal. No que concerne as alterações hepáticas e a ação da insulina, a dieta HF durante o período perinatal favoreceu 25% de esteatose hepática, hiperinsulinemia e hiperleptinemia, enquanto os demais grupos experimentais SC/HF e HF/HF, demonstraram um padrão mais exacerbado. A avaliação da distribuição e morfometria do tecido adiposo demonstra o importante papel da dieta HF perinatal em amplificar a habilidade de estocar gordura visceral na prole. Considerando a ação central da leptina nos grupos tratados, a resposta alimentar mostrou-se atenuada em SC/HF, indicando o efeito determinante da dieta pós-desmame sobre a ação da leptina nesse modelo. Os resultados indicam fortemente que a dieta HF materna afeta a saúde da prole adulta. Especificamente, a prole programada apresenta esteatose hepática, hipertrofia de adipócitos, aumento de gordura visceral, hiperleptinemia e resistência a insulina. Esse fenótipo não está associado a resistência central a leptina na prole aos três meses de idade. / Maternal high-fat diet consumption during pregnancy and lactation causes metabolic abnormalities (MA) (similar to metabolic syndrome in humans) in the rodents offspring. We tested the hypothesis that the offspring of dams fed a high fat diet during pregnancy and lactation develop MA and leptin resistance.Pregnant C57BL6 mice (n=20) were fed either standard chow (SC; 19% fat) or a high fat diet (HF; 49% fat). After weaning, male offspring were divided into four groups according to the diet of dams and offspring: SC(dams)/SC(offspring), SC/HF, HF/SC and HF/HF (n=12/group). MA were characterized by weight gain curve measured weekly; tail-cuff systolic pressure; fast glucose and areas under the curve after oral glucose tolerance test; fat mass depots; leptin and insulin concentrations, all performed at 12 weeks of age.To analyze leptin sensitivity, each group was divided into two groups (vehicle or leptin-5g) to identify the feeding response and pSTAT3 expression after acute intracerebroventricular (ICV) treatment (n=6/group). The HF schedule during post-weaning (SC/HF group), during gestation and lactation (HF/SC group), or both periods (HF/HF group), increased body mass in experimental groups. In respect to hepatic alterations and insulin action, the HF diet during gestation and lactation caused 25% of liver steatosis, hiperinsulinemia and hiperleptinemia, whereas SC/HF and HF/HF presented worst patterns. The fat distribution and morphometry pointed for the key role of HF during gestation and lactation in amplify the ability to store fat in the offspring. Considering the central leptin action in offspring treated groups, SC/HF was not responsive to leptin treatment, which strong indicates the determining effect of post-weaning diet upon leptin action in this model. The compelling results indicate that maternal HF schedule during pregnancy and lactation affects the offpring health. Specifically, programmed offspring presented liver steatosis, adipocyte hipertrophy, increased visceral fat, hiperleptinemia and insulin resistance. This phenotype was not associated with central leptin resistance in offspring at 3 month-age.

A obesidade assim como a gestação está relacionada com distúrbios dos metabolismos da glicose, lipídios, hormônios e produção de moléculas inflamatórias. Portanto, supõe-se que a obesidade na gestação pode influenciar o desenvolvimento do feto, interferindo na sua composição corporal e predispondo a doenças cardiovasculares na idade adulta. Este estudo avaliou a relação entre a composição corporal e leptina e adiponectina séricas materna e a composição corporal de neonatos. A composição corporal de 215 mães e seus respectivos neonatos foi determinada por bioimpedância segmentada e pletismografia por deslocamento de ar, respectivamente. Os níveis séricos de leptina e adiponectina maternos foram avaliados pelo método de Enzyme Linked Immuno Sorbent Assay ELISA. Utilizou-se análise de regressão univariada e análise de regressão linear múltipla para determinar a associação entre fatores maternos e composição corporal do neonato, considerando-se como variáveis resposta a massa de gordura e a massa livre de gordura do neonato. As mães apresentaram idade média de 25,9 (5,2) anos, 43,4 por cento eram pardas e 55,3 por cento pertenciam à classe econômica B. Cerca de 50 por cento das mães apresentaram Índice de Massa Corporal (IMC) pré-gestacional adequado, 27,7 por cento tinham sobrepeso e 10,8 por cento eram obesas.47,1 por cento dos partos foram normal e 29,1 por cento foram cesárea. Nasceram mais crianças do sexo feminino (55,4 por cento) que do masculino e a média de peso ao nascimento foi de aproximadamente 3373 (423) g. O IMC pré-gestacional materno, a massa livre de gordura materna, a massa muscular esquelética materna e a concentração plasmática de adiponectina apresentaram associação positiva com a massa de gordura do neonato. A massa livre de gordura materna, massa muscular esquelética materna e massa muscular do braço direito apresentaram associação positiva com a massa livre de gordura do neonato. A composição corporal materna e a adiponectina, proteína secretada pelo tecido adiposo, exercem influência sobre a composição corporal do neonato. Espera-se que mais estudos sejam conduzidos para investigar os mecanismos envolvidos nos achados desta pesquisa / Obesity as well as gestation is related to disturbances of glucose metabolism, lipids, hormones and production of inflammatory molecules. Therefore, it is assumed that obesity during pregnancy can influence the development of the fetus, interfering with its body composition and predisposing to cardiovascular diseases in adulthood. This study evaluated the relationship between body composition and maternal serum leptin and adiponectin and the body composition of neonates. The body composition of 215 mothers and their respective neonates was determined by segmented bioimpedance and air displacement plethysmography, respectively. Serum levels of maternal leptin and adiponectin were assessed by Enzyme Linked Immuno Sorbent Assay ELISA. We used univariate regression analysis and multiple linear regression analysis to determine the association between maternal factors and body composition of the newborn, considering as variables the fat mass and the fat free mass of the newborn. The mothers had a mean age of 25.9 (5.2) years, 43.4 per cent were brown and 55.3 per cent belonged to economic class B. Approximately 50 per cent of the mothers presented Body Mass Index (BMI) adequate pre-gestational age, 27.7 per cent were overweight and 10.8 per cent were obese.47,1 per cent of births were normal and 29.1 per cent were cesarean. More female children (55.4 per cent) were born than male children and the mean birth weight was approximately 3373 (423) g. Maternal pre-gestational BMI, maternal fat-free mass, maternal skeletal muscle mass, and adiponectin plasma concentration were positively associated with neonatal fat mass. The maternal fat free mass, maternal skeletal muscle mass and right arm muscle mass were positively associated with the fat free mass of the newborn. Maternal body composition and adiponectin, a protein secreted by adipose tissue, influence the body composition of the neonate. It is expected that further studies will be conducted to investigate the mechanisms involved in the findings of this research

Fatores dietéticos como o selênio (Se) são apontados como importantes moduladores do risco de desenvolvimento do câncer de mama. Essa neoplasia pode apresentar sua origem no início do desenvolvimento e, assim, a alimentação materna poderia ter importantes repercussões na programação fetal da doença. A fim de verificar se diferentes concentração de selênio na dieta materna poderiam programar o risco da progênie feminina ao câncer de mama, ratas foram alimentadas com ração contendo 0,15 (CO), 1,0 (SUP) ou 0,05 (DEF) ppm de Se durante a gestação e sua progênie feminina iniciada com DMBA. A progênie do grupo SUP apresentou menor suscetibilidade à carcinogênese, indicado pelo menor número médio e multiplicidade de adenocarcinomas mamários (p< 0,05), enquanto a do grupo DEF apresentou maior suscetibilidade à carcinogênese, indicado pela maior incidência dos mesmos (p< 0,05). Mães do grupo DEF apresentaram menor concentração de Se no sangue (p< 0,05) e sua prole apresentou menor atividade da enzima GPx1 (p< 0,05). Além disso, observou-se na glândula mamária da progênie de 50 dias menor expressão (western blot e qPCR) de ER&#945;, Her-2, EGFR e Ras no grupo SUP em comparação aos grupos CO e DEF (p< 0,05). Analisou-se, ainda, o padrão de metilação global do DNA (HPLC-DAD), expressão das enzimas DNMT1, 3a e 3b (qPCR), o padrão global de modificações pós traducionais em histonas (western blot) e o padrão de metilação da região promotora do gene Er&#945; (modificação com bissulfito e pirossequenciamento) na glândula mamária da progênie de 50 dias. Não houve diferença no padrão de metilação global do DNA e expressão das enzimas DNMTs (p>0,05). Houve aumento na expressão de H4K16 acetilada nos grupos SUP e DEF (p< 0,05). Finalmente, em comparação a progênie do grupo DEF, a do grupo SUP apresentou região promotora de Er&#945; com aumento marginal (p=0,07) na metilação de dois dinucleotídeos CpG. Conclui-se que o consumo de diferentes concentrações de Se na dieta materna tem impacto sobre a suscetibilidade da progênie ao câncer de mama na vida adulta através da modulação da expressão de receptores e oncogenes relacionados ao desenvolvimeto dessa neoplasia, além da influência em processos epigenéticos. Tais resultados apontam para a existência de uma \"janela de programação\" no início do desenvolvimento sensível a ação do Se, resultando em diminuição do risco de câncer de mama quando suplementado na dieta materna e o inverso quando de sua deficiencia. / Based on epidemiological studies and animal models, the essential micronutrient selenium has been highlighted as a promising dietary factor associated to breast cancer risk reduction. Breast cancer may have its origin in early development and thus the maternal diet could have important implications in the fetal programming of the disease. In order to ascertain whether differences in selenium concentration in maternal diet could modulate the susceptibility of female offspring to breast cancer, a biological assay was conducted in which female rats were fed a diet with 0.15 (CO), 1.0 (SUP) or 0.05 (DEF) ppm of selenium during gestational period and the female offspring subjected to a mammary carcinogenesis model induced by DMBA. SUP group offspring presented decreased susceptibility to mammary carcinogenesis, as indicated by lower (p< 0,05) average number and multiplicity od adenocarcinomas, while the DEF group offspring had a greater susceptibility, as indicated by the increase (p< 0,05) in adenocarcinomas incidency. Mothers of the DEF group pesented lower (p< 0,05) Se blood concetrations and their offspring presented lower (p<0,05).GPx1 activity. In addition, there was a decrease (p< 0,05) in ER&#945;, Her-2, EGFR and Ras expression (western blot and qPCR) in the mammary gland of 7 weeks old female SUP group offspring when compared to CO and DEF groups offspring. DNA global methylation pattern (HPLC-DAD), DNMT1, 3a e 3b expression (qPCR), global pattern of post-translational modification in histones (western blot) and methylation status of Er&#945; promoter region (bisulfite modification and pyrosequencing) were also evaluated in the mammary gland of 7 weeks old offspring. There was no diffrence (p>0,05) in DNA global methylation pattern and DNMTs expression. There was an increase in acetilated H4K16 expression in groups SUP and DEF (p< 0,05). Lastly, when compared to DEF offspring, the SUP offspring presented a marginal increase in the methylation of two CpG dinucleotides in the Er&#945; promoter region. In conclusion, the consumption of different selenium concentration in maternal diet plays a role in the progeny\'s breast cancer susceptibility through the modulation of receptors and oncogenes expression, in addition to modifications in epigenetic patterns. These results indicate the presence of a \"programming window\" in the beggining of development susceptible to selenium effects, resulting in decreased breast cancer risk when supplemented and the opposite when deficient.

>Magister Scientiae - MSc / Blood pressure and heart rate is known to increase during smoking. These effects are specifically associated with nicotine while the other components of tobacco smoke seem to be of minor importance. It is becoming increasingly clear that fetal nicotine exposure, through transfer of nicotine via the placenta, has numerous consequences that is detrimental to the health of the fetus and that these effects may last into adulthood or perhaps even manifest itself later in life. In this study, we investigated the effects of maternal nicotine exposure during pregnancy and lactation on the blood pressure of the male offspring. A preliminary study indicated that the female offspring do not become hypertensive. We were particularly interested to determine whether hypertension in the offspring could be prevented or attenuated by vitamin C (an antioxidant) therapy. When confirmed to be pregnant, female Wistar rats were divided into four groups. The control group (group 1) received saline (1ml/day, s.c), the animals in group 2 received nicotine (1mg/kg/day in ml, s.c), group 3 animals received a combination of saline (1 ml/day s.c.) and vitamin C (1g/l in drinking water) and the animals in group 4 received a combination of nicotine (1mg/kg/day, s.c) and vitamin C (1g/l in the drinking water) during pregnancy and lactation. At weaning eight animals from group 2 received vitamin C in the drinking water (1g/l) until the end of the experiment. Blood pressure and body weight were measured every two weeks for 5 months. Blood samples were collected, and serum prepared at 3 weeks and at 5 months for biochemical analysis. Total antioxidant capacity (TAC), thiobarbituric acid reactive substances (TBARS) and superoxide dismutase (SOD) assays were determined at 3 weeks; TAC was also measured at five months. After 5 months, the animals were sacrificed and abdominal aorta was excised for histological (H and E staining) and IHC (AGE) evaluation. From the data generated in this study, it was evident that maternal nicotine exposure during pregnancy and lactation increased blood pressure of male offspring but not female offspring. Exposure to nicotine during pregnancy and lactation significantly increased systolic blood pressure from 115±4.6 mm Hg in the first month to 147±6.1 mm Hg at five months (P<0.05), diastolic blood pressure was increased from 84±3.4 mm Hg in the first month to 110±7.2 mm Hg at 5 months (P<0.05) and MAP was increased from 94.8±3.8 mm Hg in the first month to 121±6.4 mm Hg at 5 months. Interestingly the MAP of the nicotine group was normal during the first two months. HR was similar in all groups at 5 weeks and 5 months. Maternal vitamin C supplementation in rats exposed to nicotine during pregnancy and lactation did not prevent development of hypertension of the offspring (MAP=121±6.4 mm Hg in the nicotine group vs 113.4±1.7 mmHg in the nicotine and vitamin C group, P>0.05). Supplementation with vitamin C in the drinking water after weaning significantly reduced blood pressure of the offspring (MAP=121±6.4 mm Hg vs 97.6±2.9 mm Hg respectively, P<0.05). No significant difference was found in any of the biochemical assays. Maternal nicotine exposure during pregnancy and lactation leads to alteration in aorta structure as evaluated by H and E staining. Structural alterations include protrusion of the intima and irregular arrangement of the vascular smooth muscle cells (VSMC) in the tunica media. Maternal vitamin C supplementation and vitamin C supplementation after weaning did not prevent the structural alteration of the aorta. Immunohistochemistry (IHC) indicated that the accumulation of AGE's in the nicotine group was stronger than in the control group. In conclusion, we show for the first time that hypertension induced by maternal nicotine exposure can be reversed after weaning by supplementation with vitamin C, an antioxidant.

>Magister Scientiae - MSc / Tobacco consumption and exposure to tobacco smoke is one of the biggest contributing factors to a growing epidemic of non-communicable diseases (NCDs), primarily cancers, diabetes, cardiovascular and chronic lung diseases which account for 63% of all deaths worldwide (WHO, 2011). An increased concern is in pregnant women who smoke. They not only expose themselves to nicotine, but also their unborn child. Cigarette smoking during pregnancy is associated with many developmental and growth complications. There are critical periods within the “program” that directs normal growth and development, during which the fetus is vulnerable to the effects of external factors. During these critical periods of development the program can be changed to increase the susceptibility of the fetal organs to disease and increased risk of adverse health consequences in adulthood. Health care professionals have tried to reduce the consumption of tobacco smoke by prescribing nicotine replacement therapy (NRT) to pregnant females as an alternative to smoking, without considering the effects of nicotine on the developing embryo and the health risk that might arise after birth. It is known that nicotine induces oxidant formation with resulting oxidative effects. This induces an overload of oxidants in the fetus and a decrease in the antioxidant capacity thereof. This may interfere with normal lung development.

Durant ces dernières années, de nombreuses études épidémiologiques ont mis en évidence que les pathologies métaboliques (obésité, diabète) et cardiovasculaires pourraient, en partie, se déterminer dès la grossesse, via des perturbations de l’environnement intra-utérin. La notion de « programmation fœtale » implique qu’une altération durant la vie fœtale perturberait le développement du fœtus et le vulnérabiliserait au développement ultérieur de pathologies. Ainsi, un enfant qui naît avec un très faible poids de naissance (inférieur à 2,4 kg) ou à l’inverse avec un poids de naissance très élevé (supérieur à 4,0 kg) est statistiquement plus vulnérable au développement de ces maladies. Pour étudier ce phénomène et tenter d’en comprendre les mécanismes, nous avons utilisé des modèles expérimentaux (rat, souris) et évalué l’action et l’expression de deux substances vasodilatatrices : le Fasudil (un inhibiteur des Rho kinases) et l’hormone apeline. Les rates gestantes traitées par le L-NAME, un inhibiteur de la NO synthase (50 mg/jour) présentaient une hypertension artérielle et leurs nouveau-nés un retard de croissance intra-utérin (RCIU) de l’ordre de 20%. L’administration aux mères de Fasudil (10 mg/jour) permettait de restaurer une pression artérielle normale en fin de gestation et améliorait considérablement la croissance fœtale des animaux exposés au L-NAME. Cependant, alors que les animaux nés avec un RCIU (nouveau-nés L-NAME) ne présentaient que peu de perturbations métaboliques à l’âge adulte, les animaux exposés au Fasudil seul étaient rapidement en surpoids, présentaient une hyperglycémie à jeun et développaient des troubles du comportement alimentaire de type hyperphagique. D’autre part, par une étude menée chez des souris obèses et intolérantes au glucose après exposition à un régime hyperlipidique, nous avons démontré que l’expression génique de l’apeline est altérée dans plusieurs organes (foie, rein, tissu adipeux) bien que l’apelinémie des souris obèses reste inchangée. Des études en voie de finalisation sont menées afin de déterminer si le système apelinergique est modulé chez des souris gestantes obèses à la fois chez les compartiments maternels et fœtaux mais aussi dans le placenta. En conclusion, nous avons démontré que l’inhibition de la voie des Rho kinases en fin de gestation programme chez la descendance un surpoids, une hyperglycémie et à une altération de la prise alimentaire. Ayant démontré que le système apelinergique est altéré chez des souris femelles obèses et intolérantes au glucose, il nous reste à déterminer si ce système est aussi perturbé en condition de grossesse associée à l’obésité maternelle. / During the last decade, many epidemiological studies have shown that adult chronic metabolic (obesity, diabetes) and cardiovascular diseases may be determined, at least in part, during pregnancy through alterations of intrauterine environment. The “fetal programming” hypothesis implies that disturbances of the fetal development (intra uterine growth restriction – IUGR or macrosomia) increase the vulnerability to develop these pathologies in adulthood. To gain more insight into the mechanisms implicated in fetal programming, we used two experimental models of rodents (rat, mouse) and evaluated first the effect of an inhibition of the Rho-kinase pathway in utero on fetal growth and postnatal development in rats. In another study performed in mice, we aimed to assess the expression of apelin and its receptor APJ in obese and glucose intolerant mice fed with a high fat diet. Using data of this preliminary study, we speculated that this signaling system may be targeted during the pregnancy of obese mothers and could be implicated into the physiopathological consequences that may affect the fetoplacental unit. We demonstrated that pregnant rats treated by L-NAME, a NO synthase inhibitor (50 mg/day) were hypertensive and that their newborns presented a dramatic IUGR. Maternal treatment with the vasodilator Fasudil (10 mg/day) restored a normal maternal blood pressure and remarkably alleviated the fetal growth of L-NAME newborns. In adults, L-NAME male rats developed mild metabolic pathologies whereas rats exposed in utero to Fasudil presented an overweight, with hyperphagia and glucose intolerance. In obese and glucose intolerant mice fed with a high fat diet, we showed that apelin gene expression was altered in several organs (liver, kidney and adipose tissue) without any variation of apelin plasma concentration. Further studies are currently performed in our laboratory to unravel the expression of the apelin/APJ pathway in pregnant obese mice and their offsprings.

Objetivou-se no presente estudo, avaliar o efeito da nutrição proteica no terço final da gestação de vacas Nelore, seguido de estratégias de suplementação e/ou alimentação de suas crias fêmeas sobre a idade à puberdade até os 18 meses. O delineamento utilizado foi o inteiramente casualizado em esquema fatorial 2x2x2; constituindo-se de: 2 manejos suplementar das vacas no pré-parto (Fase I); 2 manejos suplementar das crias (Fase II) e 2 manejos alimentar na recria (Fase IIIA). Na Fase I, 241 vacas foram suplementadas com farelos de soja na proporção de 0,5kg/vaca/dia (Tratamento 1) e 258 vacas foram mantidas sem acesso a suplementação Tratamento 2 (controle - Fase I). Cerca de metade do número de vacas e suas crias fêmeas, nascidas na Fase I, foram distribuídas em dois tratamentos na Fase II-(suplementação das crias) aos 110 dias de idade das crias, as quais passaram receber ou não uma mistura mineral proteica energética em creep-feeding, constituindo assim, os tratamentos suplementação de bezerras em creep-feeding (n =119) e controle (sem suplementação, n =122 ) na Fase II até os 205 dias de idade (desmama). Na fase III A, metade das bezerras de cada grupo na fase II foram manejados em confinamentos (n=119) e a outra metade permaneceu no pasto (Grupo controle, n = 122), até os 320 dias de idade. Na fase IIIB, todas as novilhas foram manejados juntos a pasto e submetidas a estação de monta a partir dos 440 dias aos 560 dias de idade. Os sistemas de suplementação das vacas e bezerras na fase de cria não afetaram o peso corporal, concentração de IGF-1 e percentual de peso adulto das novilhas no início da estação de monta (P > 0,05). O manejo das novilhas em confinamento na fase IIIA, aumentou o número de novilhas púberes (31,9% vs 13,9%; P < 0,01), para as novilhas alimentadas ou não em confinamento, respectivamente. Entretanto, a alimentação em confinamento não ocasionou diferença na idade que estas atingiram a puberdade. Considerando apenas as novilhas que atingiram à puberdade (n = 55) houve efeito de interação entre as fases de suplementação/alimentação e a idade à puberdade (P < 0,05). Para as vacas manejadas na Fase I, a suplementação influenciou a ciclicidade das mesmas no momento da IATF (68,9% vs 55,4%; P < 0,05), porém não ocasionou diferença no número de vacas prenhes (60,1 vs 55,3%; P > 0,05), vacas suplementadas e não suplementadas, respectivamente. Similarmente, a suplementação das novilhas em creep-feeding, não influenciou a taxa de prenhez das vacas (P > 0,05). Em conclusão, a suplementação das vacas com fontes proteicas não influenciou a idade a puberdade de novilhas até os 18 meses, sendo que o manejo alimentar em confinamento aumentou o número de novilhas púberes em relação com as manejadas no pasto. / The aim of the present study was to evaluate the effect of protein nutrition in the final third of gestation of Nelore cows, followed by supplementation strategies and / or feed their young females over the age of puberty until 18 months. The experimental design was a completely randomized factorial 2x2x2; constituting of: 2 suplementary managements of cows in pre-partum (Phase I); 2 supplementary managements of offspring (Phase II) and 2 alimentary managements during rearing (Phase IIIA). In Phase I, 241 cows were supplemented with soybean meal at the rate of 0.5 kg / cow / day (Treatment 1) and 258 cows were kept without access to supplemental Treatment 2 (control - phase I). About half of the cows and their female offspring, born in Phase I, were assigned to two treatments in Phase-II (supplementation of cubs) at 110 days of age of the offsprings, which now receive or not a mineral mix protein energy in creep-feeding, constituting, treatments supplementation in calves creep-feeding (n = 119) and control group (without supplementation, n = 122) in Phase II until 205 days of age (weaning). In phase III A, half of each group of calves in phase II were managed in feedlots (n = 119) and the other half remained in the pasture (control group, n = 122), up to 320 days of age. In stage IIIB, all heifers were managed together and submitted to the pasture breeding season from 440 days to 560 days old. Supplementation systems of cows and calves during the growing period did not affect body weight, concentration of IGF-1 and percentage of mature weight of heifers at the beginning of the breeding season (P> 0.05). The management of heifers in the feedlot phase IIIA, increased the number of pubertal heifers (31.9% vs 13.9%, P <0.01) for heifers fed in confinement or not, respectively. However, feeding in confinement caused no difference in age they reached puberty. Considering only heifers reached puberty (n = 55) there was an interaction effect between phases of supplementation / nutrition and age at puberty (P <0.05). For cows managed in Phase I, supplementation influenced the cyclicality of the same at the time of TAI (68.9% vs 55.4%, P <0.05), but caused no difference in the number of pregnant cows (60.1 vs 55.3%, P> 0.05), supplemented and nonsupplemented cows, respectively. Similarly, the addition of heifers in creep-feeding did not influence the rate of pregnancy in cows (P> 0.05). In conclusion, supplementation of cows with protein sources did not influence the age at puberty in heifers up to 18 months, and feeding management in confinement increased the number of pubertal compared with those managed on pasture.

<p>Fat supplementation has potential to improve reproductive performance and increase pregnancy rates in cattle by increasing the energy density of the diet. However, some of the positive effects of fat seem to be influenced by the type of fatty acid fed. Supplementation of omega-3 (n-3) fatty acids increase uptake of n-3 fatty acids into tissue phospholipids and can mitigate immune and inflammatory responses in favor of pregnancy maintenance in cattle. However, n-3 fatty acid supplementation in ruminants has been associated with a decrease in circulating PGF_2α, which may delay CL regression, extend an animal’s time in diestrus, and prevent ovulation. Prostaglandin F_2α is a series 2 prostaglandin, synthesized from omega-6 (n-6) fatty acids, which is inhibited by production of series 3 prostaglandins from n-3 fatty acids. Docosohexaenoic acid (DHA, 22:6n-3) and eicosapentaenoic acid (EPA, 20:5n-3) are long-chain n-3 poly-unsaturated fatty acids (PUFA) that have important biological effects on reproduction through their involvement in hormone and series 3 prostaglandin synthesis. Ruminant tissues are naturally almost devoid of n-3 long-chain PUFA, specifically EPA and DHA. Fish oil is the most common ration additive used to provide very long chain n-3 fatty acids to ruminants. However, marine fish do not synthesize n-3 fatty acids; they consume microscopic algae or other algae-consuming fish to obtain n-3 fatty acids. Algae biomass provides a consistent source of DHA and EPA that could be fed to alter hormonal profiles and improve reproduction of beef heifers. Eighty-eight Angus × Simmental heifers (427 ± 1.8 kg) were blocked by BW and allotted to 2 treatments (44/treatment, 4 pens/treatment, 11 heifers/pen). Control heifers were fed a diet that contained (DM basis) 52.8% mixed grass silage, 32% corn silage, and 15.2% concentrate. DHAgold™ (49% fat; 21.8% DHA; DSM Inc.) was included in the algae diet at 1.65% of DM, replacing equal parts of corn and DDGS. Diets were formulated to contain 12% CP and 0.79 Mcal/kg NEg. Heifers were fed treatment diets from 54 d prior to the breeding season through the first trimester. Follicular fluid was collected on day 47 for hormonal analysis. Artificial insemination (AI) was from d 55 to 98, after which open heifers were removed to 1 control and 1 algae pen and placed with a bull. The study ended on d 180. Performance data were analyzed using the MIXED procedure and conception data were analyzed using the GLIMMIX procedure of SAS. Dominant follicle diameter and follicular estrogen concentration were unaffected by treatment (<i>P</i>≥0.12). Follicular insulin-like growth factor-1 was greater in algae compared to control heifers (<i>P</i>=0.03). During the pre-breeding period, algae supplemented heifers had lesser DMI (<i>P</i>=0.006), and greater ADG (<i>P</i>=0.03) during the breeding period, while BW tended to be greater compared to control heifers on d 98 and 180 (<i>P</i>≤0.07). First service conception rate did not differ between treatments (<i>P</i>=0.67); however, second service tended (<i>P</i>=0.08) and overall conception was (<i>P</i>=0.03) lesser in algae compared to control heifers. These data suggest supplementing DHA-rich algae improved growth, but decreased conception rates of primiparous beef females.</p>