Diss. (sammanfattning) Örebro : Örebro universitet, 2006. / Härtill 4 uppsatser.

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

Les champs électromagnétiques présents dans l’environnement - qu’ils soient d’extrêmement basses fréquences ou radiofréquences - sont responsables d’expositions continuelles des populations. Toutefois, leur potentiel impact sur la santé néonatale est encore aujourd’hui mal connu, notamment en raison des difficultés des études épidémiologiques à évaluer l’exposition ubiquitaire à ces champs de façon suffisamment détaillée et précise. Le premier objectif de cette thèse était d’étudier le lien entre l’exposition maternelle aux champs électromagnétiques d’extrêmement basses fréquences et deux indicateurs de la santé néonatale : la prématurité et le petit poids de naissance pour l’âge gestationnel. Le second objectif était de construire un outil permettant une estimation quantitative de l’exposition professionnelle aux radiofréquences. Les travaux menés en réponse au premier objectif s’appuient sur les données de deux cohortes de naissances françaises. L'exposition cumulée aux champs électromagnétiques d’extrêmement basses fréquences au cours de la grossesse a été évaluée grâce à l’application d’une matrice emploi exposition. Les résultats obtenus étaient en faveur d’une absence d’association avec le risque de petit poids de naissance pour l’âge gestationnel. Une association modeste pour le risque de prématurité spontanée a été rapportée chez les mères dont l’exposition cumulée jusqu’à 28 semaines d’aménorrhée était la plus élevée. Les travaux menés en réponse au second objectif reposent sur une collaboration internationale. A partir des calendriers professionnels recueillis dans le cadre d’une étude cas-témoins internationale et de mesures d’exposition extraites de la littérature, ces travaux ont permis la création d’une première matrice emploi exposition quantitative spécifique aux hautes fréquences et applicable dans les études épidémiologiques. / Electromagnetic fields in the environment - whether extremely low frequency or radiofrequency - are responsible for continuous population exposure. However, the potential impact of exposure to electromagnetic fields on neonatal health during pregnancy is still not well known, in particular due to the difficulties for epidemiological studies to assess in sufficient detail and precision the exposure to electromagnetic fields, which is ubiquitous. The first objective of this thesis was to study the relationship between maternal exposure to extremely low frequency electromagnetic fields and two indicators of neonatal health: prematurity and small for gestational age. The second objective was to build a tool for quantitative estimation of occupational exposure to radiofrequencies. The work carried out in response to the first objective is based on data from two French birth cohorts. Cumulative exposure to extremely low frequency electromagnetic fields during pregnancy was assessed using a job-exposure matrix. The results were in favor of an absence of association with the risk of small for gestational age. However, for the risk of spontaneous prematurity, a modest association was reported among the most exposed mothers up to 28 weeks of gestation. The work carried out in response to the second objective is based on an international collaboration. On the basis of the job calendars collected in an international case-control study and exposure measurements extracted from the literature, a first quantitative job-exposure matrix to estimate occupational exposure to high frequency electromagnetic fields in epidemiological studies was created.

<p>Tobacco smoking during pregnancy and lactation is a common habit and accounts for a significant percentage of fetal morbidity and mortality worldwide. The offspring is as a result exposed to nicotine through the blood and the milk of the mother. Nicotine is thus expected to interact with the developing fetus and the offspring of mothers who smoke or use NRT for smoking cessation, resulting in the interference with normal fetal and neonatal lung development. Maternal cigarette smoke or nicotine exposure produces adverse effects in the lungs of offspring, these include / intrauterine growth retardation, low birth weight, premature birth, reduced pulmonary function at birth, and a high occurrence of respiratory illnesses after birth. This study aimed at investigating&nbsp / the effects of maternal nicotine exposure during gestation and lactation on lung development in the offspring / to establish whether tomato juice can have protective effects on the fetal lung&nbsp / development and function in the offspring / and to determine if nicotine cases premature aging of the lungs of the offspring. It was therefore shown that maternal exposure to nicotine during&nbsp / gestation and lactation ad no significant effect on the growth parameters of the offspring. Maternal nicotine exposure during gestation and lactation had no effect on the growth parameters of&nbsp / the offspring, but resulted in compromised lung structure and function. The morphometric results demonstrated decrease in alveolar number, increase in alveolar size, and decrease in lung&nbsp / parenchyma of the nicotine exposed animals showing a gradual deterioration of the lung parenchyma. Structural alterations include emphysematous lesions, where the latter was&nbsp / accompanied by an increase in alveolar size (Lm), and a decrease in the tissue volume of the lung parenchyma. Thickening of alveolar walls was also evident and serves as an indication of&nbsp / remodeling of the extracellular matrix, also a characteristic of emphysema. A consequence of the gradual deterioration of the lung parenchyma is a decrease in the alveolar surface area available for gas exchange. The present study showed that the emphysematous lesions were conceivably a result of a reduced rate of cell proliferation accompanied by the increase in&nbsp / senescent cells numbers in the alveolar walls of the exposed offspring. The data of this study suggests that maternal nicotine exposure during gestation and lactation induces premature&nbsp / aging of the lungs of the offspring rendering the lungs of the offspring more susceptible to disease later in life. Since these structural changes occurred later in the life of the offspring and long&nbsp / after nicotine withdrawal, it is suggested that it is programmed during gestation and lactation. Smoking and NRT result in an increased load of oxidants in the mother and fetus. It also reduces&nbsp / the level of anti-oxidants and thereby compromising the ability of the mother to protect the fetus. It is hypothesized that this oxidant-antioxidant imbalance will program the lungs to age&nbsp / prematurely. The supplementation of the mother&rsquo / s diet with tomato juice, rich in lycopene, other anti-oxidants such as vitamin C, as well as phytonutrients protected the lungs of the offspring&nbsp / against the adverse effects of maternal nicotine exposure. This supports the hypothesis mentioned above. The study further showed that the effects of grand-maternal nicotine exposure during gestation and lactation on the lungs of the F1 offspring is also transferred to the F2 offspring. This is most likely via the paternal and maternal germ line. Since tomato juice supplementation of the mother&rsquo / s diet with tomato juice prevented&nbsp / the adverse effects of maternal nicotine exposure on the lungs of the offspring, it is conceivable that it will prevent transfer of these changes to the F2 generation.&nbsp / </p>

Thesis (D.P.H.)--University of Alabama at Birmingham, 2007. / Title from PDF title page (viewed on Feb. 19, 2010). Includes bibliographical references.

<p>Tobacco smoking during pregnancy and lactation is a common habit and accounts for a significant percentage of fetal morbidity and mortality worldwide. The offspring is as a result exposed to nicotine through the blood and the milk of the mother. Nicotine is thus expected to interact with the developing fetus and the offspring of mothers who smoke or use NRT for smoking cessation, resulting in the interference with normal fetal and neonatal lung development. Maternal cigarette smoke or nicotine exposure produces adverse effects in the lungs of offspring, these include / intrauterine growth retardation, low birth weight, premature birth, reduced pulmonary function at birth, and a high occurrence of respiratory illnesses after birth. This study aimed at investigating&nbsp / the effects of maternal nicotine exposure during gestation and lactation on lung development in the offspring / to establish whether tomato juice can have protective effects on the fetal lung&nbsp / development and function in the offspring / and to determine if nicotine cases premature aging of the lungs of the offspring. It was therefore shown that maternal exposure to nicotine during&nbsp / gestation and lactation ad no significant effect on the growth parameters of the offspring. Maternal nicotine exposure during gestation and lactation had no effect on the growth parameters of&nbsp / the offspring, but resulted in compromised lung structure and function. The morphometric results demonstrated decrease in alveolar number, increase in alveolar size, and decrease in lung&nbsp / parenchyma of the nicotine exposed animals showing a gradual deterioration of the lung parenchyma. Structural alterations include emphysematous lesions, where the latter was&nbsp / accompanied by an increase in alveolar size (Lm), and a decrease in the tissue volume of the lung parenchyma. Thickening of alveolar walls was also evident and serves as an indication of&nbsp / remodeling of the extracellular matrix, also a characteristic of emphysema. A consequence of the gradual deterioration of the lung parenchyma is a decrease in the alveolar surface area available for gas exchange. The present study showed that the emphysematous lesions were conceivably a result of a reduced rate of cell proliferation accompanied by the increase in&nbsp / senescent cells numbers in the alveolar walls of the exposed offspring. The data of this study suggests that maternal nicotine exposure during gestation and lactation induces premature&nbsp / aging of the lungs of the offspring rendering the lungs of the offspring more susceptible to disease later in life. Since these structural changes occurred later in the life of the offspring and long&nbsp / after nicotine withdrawal, it is suggested that it is programmed during gestation and lactation. Smoking and NRT result in an increased load of oxidants in the mother and fetus. It also reduces&nbsp / the level of anti-oxidants and thereby compromising the ability of the mother to protect the fetus. It is hypothesized that this oxidant-antioxidant imbalance will program the lungs to age&nbsp / prematurely. The supplementation of the mother&rsquo / s diet with tomato juice, rich in lycopene, other anti-oxidants such as vitamin C, as well as phytonutrients protected the lungs of the offspring&nbsp / against the adverse effects of maternal nicotine exposure. This supports the hypothesis mentioned above. The study further showed that the effects of grand-maternal nicotine exposure during gestation and lactation on the lungs of the F1 offspring is also transferred to the F2 offspring. This is most likely via the paternal and maternal germ line. Since tomato juice supplementation of the mother&rsquo / s diet with tomato juice prevented&nbsp / the adverse effects of maternal nicotine exposure on the lungs of the offspring, it is conceivable that it will prevent transfer of these changes to the F2 generation.&nbsp / </p>

Thesis (Ph. D.)--University of Washington, 2005. / Vita. Includes bibliographical references (leaves 99-120).

Orientadores: Sebastião Roberto Taboga, Fernanda Cristina Alcântara dos Santos / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-25T18:00:07Z (GMT). No. of bitstreams: 1 Perez_AnaPauladaSilva_D.pdf: 9263858 bytes, checksum: 6ed11b7c4d0102ec555e0f333c5a35e7 (MD5) Previous issue date: 2014 / Resumo: Os disruptores endócrinos (DE) são agentes exógenos que interferem no funcionamento do sistema endócrino. O 17?-etinilestradiol (EE), um importante componente dos contraceptivos orais é um exemplo de DE. Alguns estudos com roedores machos e fêmeas relataram que a exposição aos DE durante o período pré-natal foi capaz de eliciar proliferações patológicas no sistema reprodutor, incluindo a próstata do animal adulto. Entretanto, pouco se sabe sobre a real ação do estrógeno nas próstatas de machos e fêmeas, principalmente quando se leva em consideração o comportamento de ambas às próstatas durante o desequilíbrio dos níveis de hormônios esteroides que ocorre na puberdade e durante o envelhecimento dessas glândulas. Assim o presente estudo, teve como objetivos avaliar por análises morfológicas, sorológicas e imunohistoquímica quais foram os efeitos da exposição à baixa dose de EE durante os períodos pré-natal e puberal sobre a próstata ventral masculina e na próstata feminina de gerbilo senil. Deste modo, nós dividimos os grupos experimentais de acordo com o período de exposição ao EE (15µg/kg/dia). EE/PRÉ durante o período pré-natal, EE/PUB durante a puberdade e o EE/PRÉ-PUB durante o período pré-natal e puberdade. A exposição à estrógenos sintéticos durante o desenvolvimento afeta o eixo hipotálamo-pituitária gonadal, alterando a produção de hormônios esteroides. Os resultados revelaram que a exposição ao EE durante o desenvolvimento prostático alterou os níveis de hormônios esteroides, diminuindo os níveis de testosterona nos machos senis dos grupos EE/PRÉ e EE-PRÉ/PUB e aumento, nas fêmeas senis do grupo EE/PRÉ. Os níveis de estradiol aumentaram nas fêmeas do grupo EE/PRÉ-PUB. A interação epitélio-estroma também foi afetada pela exposição ao EE durante o desenvolvimento, dado evidenciado pela diminuição da imunorreatividade de ?-actina de músculo liso em regiões com presença de lesões invasivas, principalmente na próstata ventral de macho senil. A frequência de células positivas de p63 diminuiu na próstata ventral masculina do grupo EE/PRÉ, provavelmente a camada basal diminui em locais onde se observa foco com NIP e, aumentou na próstata feminina do grupo EE/PUB. Entretanto, esses dados mostraram que a próstata ventral de machos senil foi mais sensível aos efeitos da exposição ao EE, comparado à próstata de fêmeas senis. A senescência é caracterizada pela queda dos hormônios sexuais¸ e nessa fase aumenta as doenças prostáticas em machos e fêmeas. A exposição ao EE durante fases críticas como o pré-natal e a puberdade acentuaram as alterações na estrutura glandular da próstata e aumentaram o desenvolvimento de lesões prostáticas na senescência. Assim como o período pré-natal, o puberal também foi considerado uma fase crítica na exposição ao EE sobre a próstata de gerbilos machos e fêmeas senis. O consumo de EE durante a gestação ou na puberdade altera significativamente a saúde prostática masculina e feminina durante o envelhecimento, e o gerbilo foi considerado um bom modelo para esse estudo / Abstract: Endocrine disruptor (ED) are exogenous agents that interfere in the endocrine system function. 17?-ethinylestradiol, an important component of oral contraceptives is an example of ED. Studies with male and female rodents have reported that exposure to ED during the prenatal period is able to elicit aberrant pathological proliferations in the reproductive system, inclusive in the prostate of the adult animal. However, the amount known about the actual action of estrogen on male and female prostate, mainly as is the behavior of both prostates during imbalance between androgen and estrogen that occurs in pubertal period and during senescence of these glands. Thus the present study aimed to evaluate by morphological, serological, histopathological and immunohistochemical methods, as the exposure to low dose of ethinylestradiol during the prenatal and pubertal periods acts on ventral male prostate and female prostate of senile gerbil. Thus, we divided the experimental groups according to the period of exposure to EE (15?g/kg/day). EE/PRE during the prenatal period, EE/PUB during puberty and EE/PRE-PUB during the prenatal period and puberty. Exposure to synthetic estrogens during development affects the hypothalamic-pituitary-gonadal axis this alters the production of steroid hormones. The results showed that exposure to EE during developing prostate changed steroid hormones levels, decreasing testosterone levels in senile male of EE/PRE and EE-PRE/PUB groups and increased in senile female of EE/PRE group. The estradiol levels enhanced in females of EE /PRE-PUB group. In addition, EE exposure during the prenatal and pubertal periods altered the immunoreactivity of AR, ER? and ER?, as the function of these receptors are critical for prostate development, changes these signaling pathways contributed to increase of development of lesion and inflammation prostate in males and females during senescence. The stromal-epithelium interaction was also affected by exposure to EE during developing, was observed by decreased immunoreactivity of smooth muscle ?-actin in regions where noted invasive lesions, mainly in the ventral male prostate of senile gerbil. Frequencies positive cells of p63 decreased in the ventral male prostate of EE/PRE group, the basal layer decreases in locals with NIP focus, and these frequencies increased the female prostate EE/PUB group. However, these data showed that the ventral male prostate of senile gerbil was more sensible to effects of exposure to EE compared to female prostate. Senescence is characterized by reducing of sexual hormones, in this phase increases the prostatic diseases in males and females. Exposure to EE during critical periods as prenatal and puberty accentuated the changes in prostate glandular structure and increased the developing prostatic lesions in senescence. As prenatal period, pubertal was also considered a critical phase during the exposure to EE on male and female prostate of senile gerbil. The use of EE during gestational or puberty phases significantly alters male and female prostate health during aging, and the gerbil was considered a good model for this study / Doutorado / Biologia Celular / Doutor em Biologia Celular e Estrutural

>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.

Philosophiae Doctor - PhD / exposed to nicotine through the blood and the milk of the mother. Nicotine is thus expected to interact with the developing fetus and the offspring of mothers who smoke or use NRT for smoking cessation, resulting in the interference with normal fetal and neonatal lung development. Maternal cigarette smoke or nicotine exposure produces adverse effects in the lungs of offspring, these include; intrauterine growth retardation, low birth weight, premature birth, reduced pulmonary function at birth, and a high occurrence of respiratory illnesses after birth. This study aimed at investigating the effects of maternal nicotine exposure during gestation and lactation on lung development in the offspring; to establish whether tomato juice can have protective effects on the fetal lung development and function in the offspring; and to determine if nicotine cases premature aging of the lungs of the offspring. It was therefore shown that maternal exposure to nicotine during gestation and lactation ad no significant effect on the growth parameters of the offspring. Maternal nicotine exposure during gestation and lactation had no effect on the growth parameters of the offspring, but resulted in compromised lung structure and function. The morphometric results demonstrated decrease in alveolar number, increase in alveolar size, and decrease in lung parenchyma of the nicotine exposed animals showing a gradual deterioration of the lung parenchyma. Structural alterations include emphysematous lesions, where the latter was accompanied by an increase in alveolar size (Lm), and a decrease in the tissue volume of the lung parenchyma. Thickening of alveolar walls was also evident and serves as an indication of remodeling of the extracellular matrix, also a characteristic of emphysema. A consequence of the gradual deterioration of the lung parenchyma is a decrease in the alveolar surface area available for gas exchange. The present study showed that the emphysematous lesions were conceivably a result of a reduced rate of cell proliferation accompanied by the increase in senescent cells numbers in the alveolar walls of the exposed offspring. The data of this study suggests that maternal nicotine exposure during gestation and lactation induces premature aging of the lungs of the offspring rendering the lungs of the offspring more susceptible to disease later in life. Since these structural changes occurred later in the life of the offspring and long after nicotine withdrawal, it is suggested that it is programmed during gestation and lactation. Smoking and NRT result in an increased load of oxidants in the mother and fetus. It also reduces the level of anti-oxidants and thereby compromising the ability of the mother to protect the fetus. It is hypothesized that this oxidant-antioxidant imbalance will program the lungs to age prematurely. The supplementation of the mother’s diet with tomato juice, rich in lycopene, other anti-oxidants such as vitamin C, as well as phytonutrients protected the lungs of the offspring against the adverse effects of maternal nicotine exposure. This supports the hypothesis mentioned above. The study further showed that the effects of grand-maternal nicotine exposure during gestation and lactation on the lungs of the F1 offspring is also transferred to the F2 offspring. This is most likely via the paternal and maternal germ line. Since tomato juice supplementation of the mother’s diet with tomato juice prevented the adverse effects of maternal nicotine exposure on the lungs of the offspring, it is conceivable that it will prevent transfer of these changes to the F2 generation. / South Africa