Orientadoesr: Patrícia Aline Boer, José Antônio Rocha Contijo / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-21T03:17:34Z (GMT). No. of bitstreams: 1 Oliveira_AgnesdaSilvaLopes_M.pdf: 2796027 bytes, checksum: 870f793968de3a84abd8d4b40ecd4034 (MD5) Previous issue date: 2012 / Resumo: Estudos têm demonstrado que a deficiência de nutrientes durante a gravidez ou nos primeiros anos de vida pós-natal resultam em anormalidades estruturais no hipocampo da prole, bem como comprometimento cognitivo em animais com 16 semanas de vida. Na tentativa de analisar se a restrição protéica gestacional pode induzir a déficits de aprendizagem e perda de memória associada a alterações estruturais no hipocampo, realizou-se teste de water maze (MWM) e uma análise detalhada morfométrica da citoarquitetura dendrítica do hipocampo de ratos machos adultos. Além disso, analisamos no hipocampo dorsal e ventral a expressão e localização de receptores de mineralocorticóides (MR) e glicocorticóides (GR), angiotensina II receptor tipo 1 (AT1) e receptores específicos de serotonina (5HT1A e 5HT2A). No MWM não foram encontradas diferenças significativas entre os grupos LP e NP, em qualquer um dos parâmetros analisados no teste de memória espacial, sugerindo que tais funções de hipocampo não foram alteradas com a restrição proteica gestacional. No entanto, através da aplicação da técnica de Gogi-Cox realizamos a reconstrução dendrítica nos neurônios do hipocampo dorsal. Nossos resultados demonstram que a restrição proteica gestacional leva a uma diminuição do comprimento dos dendritos basais e no número de intersecções dos dendritos apicais de CA3. A citoarquitetura de CA1 e do giro denteado não foi alterada. O presente estudo revelou uma clara dissociação entre a resposta do teste comportamental e alterações de neurônios do hipocampo, como conseqüência da programação fetal. Encontramos diferentes padrões de expressão dos receptores analisados no hipocampo dorsal e ventral o que sugere que redução na expressão de GR e 5HT1A paralelamente a maior expressão de 5HT2A estão envolvidos no comportamento ansioso e que a significativa diminuição na expressão de AT1 pode ter um efeito protetor. Essas alterações neuroquímicas podem ter consequências importantes para comportamento de ansiedade e depressão. Nosso estudo não é capaz de responder se as alterações encontradas estão relacionadas com subdesenvolvimento no útero ou resulta de uma adaptação pós-natal para a fisiologia programada na vida adulta. Outros estudos devem ser feitos para responder essas questões / Abstract: Studies have demonstrated that maternal nutritional restriction during pregnancy or in early postnatal life results in hippocampus cognitive impairment and structural abnormalities in the 16-wk-old offspring. In an attempt to analyze whether gestational protein restriction might induce learning and memory impairment associated with structural changes in the hippocampus we carried out MWM test and a detailed morphometric analysis of dendritic cytoarchitecture of the hippocampus from male adult rats. In addition, we analyzed the dorsal and ventral hippocampal expression and localization of mineralo- (MR) and glucocorticoid (GR), type 1 angiotensina II receptor (AT1) and serotonin specific receptors (5HT1A and 5HT2A). By MWM we did not found significant differences between LP and NP groups, in any of the parameters analyzed, suggesting that such functions of hippocampus were not altered by gestational protein restriction. However, by applying 3-dimensional analysis of dendrites from the dorsal hippocampus, this study demonstrates that gestational protein restriction leads to decreases in total basal dendritic length and inapical intersections of CA3 pyramidal neurons. The dendritic architecture of CA1 and dentate gyros was unchanged. The current study revealed a clear dissociation between behavioral test response and hippocampal neuron changes as consequence of fetal programming. We found different patterns of dorsal and ventral expression of analyzed receptors and we suggests that reduced GR and 5HT1A and enhanced 5HT2A expression are involved in anxious behavior and that AT1 down regulation may has a protective effect. These neurochemical alterations may have important consequences for anxiety- and depressive-like behavior. Our study is not able to answer the question whether these alterations are related to in uteri underdevelopment or results from a postnatal adaptation to programmed physiology in adult life. Further time-course studies should be done to answer this question / Mestrado / Clinica Medica / Mestre em Clinica Medica

Orientador : Vanda Maria Gimenes Gonçalves / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-01T18:23:55Z (GMT). No. of bitstreams: 1 Muniz_IracemaAugustaCarvalhoCortez_M.pdf: 2288961 bytes, checksum: b7aa0c94a3696bccc069d6b6fb127c46 (MD5) Previous issue date: 2002 / Resumo: A desnutrição intra-uterina é responsável direta por parcela significativa da morbimortalidade no período neonatal e por repercussões em longo prazo no desenvolvimento neuropsicomotor. O presente estudo teve por objetivo avaliar o desenvolvimento neuropsicomotor no sexto mês de vida em lactentes a termo, pequenos para a idade gestacional e sua correlação com o fluxo sangüíneo cerebral por ultra-sonografia doppler ao nascimento. O trabalho foi realizado em 60 recém-nascidos a termo, selecionados no Centro de Atenção Integral à Saúde da Mulher da Universidade Estadual de Campinas, e divididos em dois grupos conforme a adequação peso/idade gestacional. O grupo 1 foi constituído por 36 recém-nascidos adequados para a idade gestacional e o grupo 2 por 24 recém-nascidos pequenos para a idade gestacional. Foram realizadas avaliações Dopplerfluxométricas entre 24 e 48 horas de vida em todos os recém-nascidos e acompanhamento posterior em 28 recém-nascidos no sexto mês de vida, sendo 16 adequados para a idade gestacional e 12 pequenos para a idade gestacional, com avaliações do neurodesenvolvimento através do instrumental das Escalas Bayley de Desenvolvimento Infantil II (BSID-II) (1993), no Laboratório de Estudos do Desenvolvimento Infantil I, do Centro de Estudos e Pesquisas em Reabilitação "Prof. Dr. Gabriel Porto", da Faculdade de Ciências Médicas da Universidade Estadual de Campinas. Os valores medianos de velocidade de fluxo cerebral: Velocidade de Fluxo no Pico Sistólico (VFPS), Velocidade de Fluxo no Final da Diástole (VFFD), Velocidade Média de Fluxo (VMF), mensurados em Artéria Cerebral Anterior (ACA) foram menores no grupo 2. Houve significância estatística com relação às velocidades sistólica e média. Resultados semelhantes foram observados em Artéria Cerebral Média (ACM), sem diferenças significativas. Constatou-se que a adequação peso/idade, a presença de policitemia neonatal e os valores de pressão arterial média estiveram associados aos valores de VMF em ACA. Enquanto a presença de sofrimento fetal, os valores de pressão arterial média e o hábito de fumar durante a gestação estiveram associados ao fluxo médio em ACM. A avaliação do neurodesenvolvimento demonstrou valores menores de ¿Index Score¿ em RN PIG, sem significado estatístico, havendo associação significativa entre o fluxo em ACA nas medidas de VFPS com a Escala Mental e Motora e da VMF com a Escala Motora. Não houve correlação de fluxo em relação à ACM. Concluiu-se que os RN PIG apresentaram valores de fluxo sistólico e médio significativamente menores em ACA, sendo observado um modelo de alta complexidade, não dependendo apenas da condição de nutrição ao nascimento. A performance do neurodesenvolvimento esteve associada significativamente aos valores de VFPS em ACA nas Escalas Mental e Motora e com a VMF em ACA na Escala Motora / Abstract: The intrauterine malnutrition is responsible not only for a great number of morbidity and mortality in neonatal period but also for causing neurological and intellectual sequelae. This paper aimed to evaluate the neurological development of full term infants, small-for-gestational age, and the correlation with cerebral blood flow using cranial ultrasound Doppler at birth. This study was performed at CAISM, a center for pregnant women, at the School Hospital of State University of Campinas (UNICAMP). Sixty term infants were selected and divided in two groups: Appropriate-for-gestational age (AGA) (36) and Small-for-gestational age (SGA) (24). Cranial ultrasound Doppler evaluation was performed on both groups, between 24 and 48 hours after birth. Twenty-eight subjects were followed at six months at LEDI I / CEPRE, a center for treating children with physical disability, using the Bayley Scales of Infant Development II (BSID II). Cerebral Blood Flow Velocity (CBFV), comprising Peak Systolic Flow Velocity (PSFV), End Diastolic Flow Velocity (EDFV), Mean Flow Velocity (MFV), was inferior in the small-for-gestational group, in the Anterior Cerebral Artery (ACA). Doppler measurements were statistically significant in the second group only for values related to Peak Systolic Flow Velocity and Mean Flow Velocity in the ACA. Similar results were seen in the Middle Cerebral Artery (MCA). However, there was no difference for any evaluated parameters of flow velocity in such artery. As to cerebral blood flow influencing factors, it was observed that weight/gestational age (AGA or SGA), presence of neonatal polycythemia and mean arterial blood pressure were statistically related to Mean Flow Velocity in the ACA. In presence of fetal suffering, mean arterial blood pressure and smoking in the pregnancy were statistically related to Mean Flow Velocity in the MCA. Index Score values were inferior in the small-for-gestational age newborns at six months. There was a significant association of Peak Systolic Flow Velocity with Mental and Motor Scales in the ACA and there was also a significant association of Mean Flow Velocity in the ACA with Motor Scales. There was no association for any evaluated parameters of flow velocity in the MCA. We concluded that small-for-gestational age newborns present Peak Systolic Flow Velocity and Mean Flow Velocity significantly reduced only in the Anterior Cerebral Artery. Results show that cerebral blood flow in newborns can be a highly complex model, which does not depend only on the intrauterine growth. The neurological development of small-for-gestational age was significantly associated to PSFV values in ACA in Mental and Motor Scales, and to MFV in ACA in Motor Scale / Mestrado / Pediatria / Mestre em Saude da Criança e do Adolescente

Made available in DSpace on 2014-06-12T22:57:31Z (GMT). No. of bitstreams: 2 arquivo2785_1.pdf: 6843043 bytes, checksum: a6f702ab6c00652094883997742e770c (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2009 / Insultos ocorridos em um período crítico no início da vida, como na gestação e/ou lactação, atuam como fator de impressão e podem repercutir em alterações fisiológicas na idade adulta, estabelecendo o futuro estado metabólico e hormonal da progênie, sendo este efeito denominado programação . A desnutrição materna parece reduzir a proliferação de mioblastos e a formação de fibras musculares do feto em desenvolvimento. Este estudo teve como objetivo verificar o efeito do treinamento físico moderado na morfologia de fibras dos músculos sóleo e extensor longo dos dedos (EDL) de animais submetidos à desnutrição por dieta baixa em proteína durante a gestação e lactação. Ratos machos Wistar (60 dias de idade) provindos de mães desnutridas durante a gestação e lactação (8% de caseína, n=5) ou controle (17% caseína, n=5), foram divididos em 4 grupos: controle (Cf, n=6), desnutrido (Df, n=6), controle treinado (CTf, n=6) e desnutrido treinado (DTf, n=6). O programa de treino consistiu em 8 semanas, 5 dias/semana, 60 min/dia a 70% do VO2max. O peso corporal e a taxa de crescimento foram avaliados diariamente durante o experimento. Após o período de treinamento, os músculos sóleo e EDL foram retirados para análise histológica dos tipos de fibras pelo técnica de ATPase. Os animais Df apresentaram uma diminuição de 60% na taxa de crescimento até os 60 dias de idade. A partir dos 60 dias, o grupo Df apresentou um aumento no ganho de peso corporal. No músculo EDL, o grupo CTf apresentou um aumento do percentual de fibras do Tipo IIa (CTf = 68,8 ± 0,7; Cf = 59,5 ± 1,1; p<0,05) e uma diminuição no percentual de fibras do Tipo IIb (CTf = 32,2 ± 0,6; Cf = 36,7 ± 1,1; p<0,05). Este mesmo resultado ocorreu para o grupo DTf quando comparado ao seu controle Df. No músculo sóleo, o grupo Df apresentou uma diminuição no percentual de fibras do tipo I (Df = 77,8 ± 0,5; Cf = 83,1 ± 0,5; p<0,05) e um aumento no percentual de fibras do tipo IIa (Df = 19,0 ± 0,4; Cf = 12,9 ± 0,4; p<0,05). Os animais do grupo DTf apresentaram um aumento no percentual de fibras do tipo I (80,3 ± 0,7) e uma diminuição no percentual de fibras do tipo IIa (17,2 ± 0,7) quando comparados ao grupo Df. Em conclusão, a desnutrição hipoprotéica durante a gestação e lactação tem efeito programador na proporção dos tipos de fibras musculares nos animais adultos. O treinamento físico moderado pode atuar como estímulo ambiental para as mudanças fenotípicas em fibras de músculos mantendo a proporção de fibras oxidativas e afetando minimamente a proporção de fibras glicolíticas mesmo em animais programados pela desnutrição

M.Tech. (Radiography) / Monitoring the growth and wellbeing of the foetus is a major purpose of antenatal care. The use of diagnostic ultrasound to assess foetal wellbeing has become an important part of prenatal care in both low and high risk pregnancies. Pre-eclampsia and foetal growth restriction (FGR) remains important causes of maternal and perinatal mortality and morbidity. Pre-eclampsia is characterised by an abnormal vascular response to placentation and is a multisystem disorder of unknown cause specific to pregnancy which affects the health of both mother and fetus. Prep-eclampsia complicates between 2 and B % of all pregnancies and is the second most common cause of maternal deaths in the developing world. The aim of this study was to assess the sensitivity of uterine artery spectral Doppler screening in the prediction of pregnancies with a high risk of developing pre-eclampsia or FGR before the clinical onset of the disease. The research objectives were to: 1) Determine the sensitivity of first and second trimester uterine artery spectral Doppler assessment in predicting pre-eclampsia or FGR Identify associations between normal and abnormal uterine artery Doppler waveforms and pregnancy outcomes. 2) Determine the most effective Doppler indices 3) Develop ultrasound management guidelines The data was statistically analyzed to determine the sensitivity of uterine artery Doppler screening. In this study uterine artery Doppler screening performed well. in the risk assessment of the most severe cases of pre-eclampsia and FGR. A larger prospective multicenter trial in South Africa is long overdue and therefore a follow-up study to assess Doppler as a screening tool in a high risk population, as per the guidelines formulated.

In this thesis I used Caenorhabitis elegans as a model of Fetal Alcohol Spectrum Disorder (FASD) to study the physical and behavioral effects of ethanol exposure during embryonic development. Davis et al. (2008) found that ethanol exposure during larval development in C. elegans produced physical/developmental and behavioral effects; however, whether exposure during embryonic development might produce similar outcomes remained to be elucidated. Because the type and degree of effects caused by developmental ethanol exposure was dependent on the pattern of ethanol treatment, in the first part of the thesis I investigated the physical/developmental effects of embryonic exposure to various ethanol doses, exposure durations, onsets and frequencies. I found that exposure to >30% ethanol for an hour during embryonic development was necessary to lower hatch rate, delay reproductive onset, and reduce body size in C. elegans. Furthermore, exposure during early embryonic development caused a larger effect than exposure during later stages, and multiple exposures produced a worse outcome than a single exposure for a comparable duration. In the second part of the thesis, I investigated locomotory activities and habituation of adult C. elegans exposed to various patterns of embryonic ethanol treatment. I found that the rate of locomotion was altered differently by chronic and acute embryonic ethanol exposure, but I did not find any effect in short- or long-term habituation. In summary, I have characterized the pattern of embryonic ethanol exposure necessary to produce physical/developmental effects in C. elegans, and identified the types of exposure conditions that would cause worse outcomes than others; in addition, I have found that embryonic ethanol exposure affects the rate of locomotion in C. elegans. In this thesis, I have established a foundation for the future investigation into the physical and motor defects caused by embryonic ethanol exposure in C. elegans. / Medicine, Faculty of / Graduate

Abstract Several in vitro methods using both human and animal tissues have been developed to study hepatic metabolism and placental transfer. The pressure to minimize animal studies has increased during the past few decades due to the public opinion and ethical considerations. However, these methods need further evaluation of their predictive power when applied in vivo. The aim of this work was to produce new information of the metabolism and transplacental passage of several anticonvulsants as well as to evaluate the usefulness of the placental perfusion method and several in vitro methods for analyzing metabolism in the prediction of clinical pharmacokinetics. Carbamazepine (CBZ) metabolism was studied using human and mouse liver microsomes, human hepatocytes, human liver slices and yeast cells expressing recombinant enzymes. All test systems predicted well the major metabolite carbamazepine-10,11-epoxide (CBZ-E). Also, minor metabolites were produced in slightly variable amounts in all systems except cells with recombinant enzymes. All human liver systems demonstrated that CYP3A4 is the principal CBZ metabolising enzyme. However, our results on CBZ-treated mice suggested that the metabolism of CBZ to CBZ-E is mainly mediated by CYP1A1 in C57/BL6 mice. Autoinduction of CBZ metabolism was seen in hepatocytes and in incubations using microsomes from CBZ-treated mice. Human liver and mouse liver microsomes metabolized oxcarbazepine (OCBZ) mainly to its active metabolite, 10-hydroxy-10,11-dihydro-carbamazepine (10-OH-CBZ). Also, 10,11-trans-dihydroxy-10,11-dihydro-carbamazepine (10,11-D) and an unknown metabolite were detected. Placental transfer of lamotrigine (LTG) and diazepam (DZP) was considerable in the human placental perfusion system, indicating marked fetal exposure in vivo. The OCBZ, 10-OH-CBZ and 10,11-D analyzed from maternal venous and cord blood also suggested significant fetal exposure. The placental perfusion system predicts well the transplacental passage of LTG and OCBZ and its major metabolite. However, in vivo cord blood concentrations of DZP are higher than maternal concentrations. Placental perfusion studies did not predict this. Still, even with its limitations, the human placental perfusion method provides information that can be used to evaluate the risk factors associated with drug use during pregnancy because understanding of specific transport characteristics is a good basis for rational risk assessment. In conclusion, all of the tested in vitro systems were useful in the prediction of at least some aspects of in vivo pharmacokinetics and metabolism, but validation and refinement are still essential, as is also the need to keep in mind the limitations characteristic of each in vitro method.

During normal placental development, a primitive vascular network develops through vasculogenesis and angiogenesis, and is then remodelled through maturation and regression. The mechanism behind this regression is unknown, but data from other systems suggests that it could be due to an endothelial-mesenchymal transition (EndMT). If this is the case, then dysregulated EndMT could lead to increased vascular regression, which could result in placental hypovascularisation. As the placental vasculature is the area of exchange between maternal and fetal circulations, a reduction in its surface area could result in fetal growth restriction (FGR). The hypothesis of this thesis is that EndMT occurs during normal placental development, but is increased during FGR and contributes to placental hypovascularisation. A primary cell model consisting of endothelial and mesenchymal cells was isolated from human first trimester placental villous stroma. These cells were shown to lose CD31 mRNA (n = 1-3) and protein (n = 15) over 4 passages, with no loss of cell viability (n = 8). EndMT-associated transcription factors were also present in these cells at all 4 passages (n = 2-4). When cells were isolated from this mixed cell model based on their CD31-positivity and examined immediately after isolation, a small proportion also expressed αSMA (n = 5). Co-expression of endothelial and mesenchymal markers suggests that an EndMT was occurring. After 24 hours in culture, the proportion of these cells expressing αSMA increased (n = 5), and some cells co-expressed vWF and αSMA, while others lost their CD31-positivity, indicating that these cells had undergone EndMT. Cells isolated based on their CD31-positivity were treated with factors shown to inhibit EndMT in other systems. However, culture with 10µM SB431542 (TGFβ receptor inhibitor; n = 6), 10µM Dorsomorphin (BMP receptor inhibitor; n = 3), or 0.1µM PDGFR-β Tyrosine Kinase Inhibitor IV (n = 3) did not inhibit gain of αSMA by these cells. Culture on Matrigel in endothelial growth medium containing VEGF and FGF also failed to stabilise the endothelial phenotype (n = 3). The possibility that EndMT occurs in placenta in vivo was examined; genes associated with EndMT were shown to be present in placenta (n = 5), and there was limited evidence of CD31 or vWF co-expression with αSMA in tissue. Preliminary evidence was obtained to suggest that expression of EndMT-associated genes was altered in FGR placentas compared to normal. In summary, the data presented in this thesis demonstrate that an EndMT occurs in primary placental microvascular endothelial cells in vitro. Furthermore, these studies provide evidence to suggest that this transition also occurs in vivo and could be altered in placentas from pregnancies complicated by FGR.

Advanced maternal age (AMA) is defined as childbearing in mothers ≥35 years of age and is becoming increasingly prevalent in high income countries. AMA has been associated with increased risk of adverse pregnancy outcomes, particularly stillbirth. Although AMA mothers have higher rates of chromosomal abnormalities and maternal co-morbidities, AMA remains an independent risk factor for stillbirth. Despite these findings, the etiology behind this increased risk is unknown. We hypothesise that an altered maternal environment, including increased oxidative stress and inflammation, due to ageing causes placental dysfunction which increases AMA mothers’ vulnerability to stillbirth. A holistic approach was applied to investigate placental dysfunction in AMA. Firstly, a systematic review and meta-analysis comprehensively reviewed existing data on AMA and associated adverse pregnancy outcomes. Secondly, Manchester Advanced Maternal Age Study (MAMAS), a multi-centre prospective observational cohort study, was conducted to investigate risk factors for composite adverse pregnancy outcome (CAPO) in AMA. MAMAS utilised both uni- and multivariate analysis on demographic and clinical data, and measuring biomarkers of ageing and placental dysfunction by ELISA in maternal circulation during the third trimester of pregnancy. Utero-placental dysfunction was directly investigated in uncomplicated AMA pregnancies by quantifying placental morphology, placental nutrient transport capabilities and both placental and maternal uterine vascular responses. Finally, a C57BL/6J murine model of AMA was developed and characterised to further investigate maternal age on pregnancy outcome and the role of the placenta. In the meta-analysis, maternal age was linearly associated with increased risk of stillbirth and other adverse outcomes strongly associated with placental dysfunction (fetal growth restriction, preeclampsia and placental abruption). In MAMAS, smoking status and primiparity were predictive of CAPO. After adjustment, AMA mothers had an odd ratio of 2.05-3.43 of CAPO compared to 20-30 year old mothers. AMA mothers showed evidence of increased oxidative stress and pro-inflammatory bias. AMA mothers who suffered CAPO showed reduced placental endocrine capacity seen in placental dysfunction. Placentas from uneventful AMA pregnancies showed evidence of accelerated ageing and placental adaptation with increased nutrient transport, increased placental weight but reduced efficiency, and altered vascular function. AMA mice showed many similar aspects to human AMA with increased fetal loss, fetal growth restriction and increased placental size. These studies provide robust evidence for increased incidence of adverse pregnancy outcome due to placental dysfunction in pregnancies of women of AMA. This finding requires the appropriate recognition in a clinical context, with a greater focus on personalised obstetric care in an attempt to reduce stillbirth rates in this high risk population. By optimising antenatal and obstetric care for AMA mothers, we could reduce stillbirth rates by 4.7% - the population attributable risk due to AMA. These studies highlight key areas of future research that will further understanding into stillbirth risk in AMA pregnancy, test predictive models and test therapies and clinical care interventions an ultimately improve pregnancy outcome in mothers of AMA.

The goal of a cow-calf producer is to produce a calf each year per cow. Research suggests that first year heifers struggle breeding back with their second calf because of the adjustments to new range/main herd conditions and the partitioning of nutrients between gaining weight, milk production, and gestation. This study was conducted at the V-V ranch at the University of Arizona for five years and looked at the effects on young cows when calves were weaned from first year heifers at 80 days rather than 205 days. Early weaning allows for gestational benefits because they are given the opportunity to adapt to herd conditions by applying feed resources to the in utero fetus and their own body condition rather than lactation. All first year heifers were included over three years, and were randomly assigned to two groups, normal weaning (NW) or early weaning (EW). This resulted in 122 heifers in the group whose calves were EW and 119 heifers in the group whose calves were NW. Heifers that were in the EW group bred back at a 27% higher rate in their second year, and had 15% greater longevity in the herd. Calves that were in utero when the nursing calves were early weaned were 16.4 kg heavier at weaning. Part of this was due to the age of the calf and part to gestational health. Early weaning was an effective strategy for improving reproductive performance of first year heifers as well as their survival rate in the herd to 5 years of age. It also resulted in improved performance for their in utero calves.

Magister Scientiae (Medical Bioscience) - MSc(MBS) / Several studies conducted in laboratories at the University of the Western Cape has demonstrated an interference with the parenchymal lung tissue of the offspring when exposed to nicotine (smoking cigarettes and/or Nicotine Replacement Therapy [NRT]), maternally i.e. during gestation and lactation. This in turn, decreases the amount of air sacs (alveolar number) resulting in a reduced surface area available for efficient gas exchange in the offspring. Since the foetus and offspring are only exposed to nicotine during gestation and lactation, emphysema- like lesions appear to develop after nicotine withdrawal in the foetus. It has been proposed that during lung development in utero, a change in the "program" that controls the maintenance of lung integrity will occur in the long term due to the initial maternal nicotine exposure. Therefore, animals that were exposed to maternal nicotine resemble lungs that have undergone rapid, premature aging caused by cellular senescence. Furthermore, energy metabolism and structural changes in the glycolytic pathways appear irreversibly slower compared to animals that were not exposed to nicotine via the mother during gestation and lactation, resulting in a reduction in the anti-oxidant capacity of lung development. Previous studies have also shown that strong anti-oxidants supplemented by smoking mothers during gestation and lactation could possibly resist change in the "program" which controls lung development and integrity of the offspring in the long term. Lycopene – as a strong anti-oxidant supplementation have shown to decrease the alveolar volume and increase the alveolar surface area for better gas exchange after the offspring has been exposed to maternal nicotine. In this study I have treated pregnant wistar rats with nicotine, tomato juice (containing lycopene among other phytonutrients), and a combination of nicotine and tomato juice during gestation, to determine various changes in the lung structure and signs of premature aging in the lungs of the offspring. I have also performed various staining techniques such as H&E, connective tissue and β- galactosidase staining which indicated whether maternal nicotine exposure indeed induced premature cellular senescence in the lungs of the offspring. / National Research Foundation