Thesis (Ph. D.)--University of Washington, 1999. / Vita. Includes bibliographical references (leaves [105]-131).

Polycystic ovary syndrome (PCOS) is one of the most common and complex endocrinopathies among reproductive-aged women. Symptom heterogeneity among clinical cases and in sibling studies suggests that PCOS is a multifactorial disease with environmental components. Investigators hypothesize that endocrine disruptors may contribute to the pathophysiological origins of PCOS in utero. The goal of this literature review is to present and compare the available research investigating the developmental origins of PCOS deriving from prenatal exposure to three major classes of endocrine disruptors: bisphenol A (BPA), phthalates, and androgenic endocrine disruptors. Considerable evidence has been found to suggest links between fetal exposure to endocrine disruptors and PCOS. Rodent studies reported that maternal BPA exposure dysregulates postnatal development and sexual maturation. In rats, gestational exposure to dibutyl phthalate (DBP) and di(2-ethylhexyl)phthalate (DEHP) resulted in polycystic ovaries among first and third generation offspring. Additionally, serum DBP concentrations are higher among women with PCOS. Regarding DEHP, animal studies have shown that prenatal exposure results in an endocrinological profile similar to PCOS. Nicotine and 3,4,4'-trichlorocarbanilide (TCC) are known androgenic endocrine disruptors. Inducing prenatal exposure to excess androgens in animal models has successfully recreated a PCOS-like phenotype that includes abnormal ovarian function, anovulatory cycling, impaired fertility, and increased visceral fat distribution. Based on the literature, endocrine disruptors appear to have an etiological role in PCOS development through prenatal exposure and thus may pose one of the greatest hazards to fetal health and development.

Orientador: Patrícia Aline Boer, José Antonio Rocha Gontijo / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-20T01:38:21Z (GMT). No. of bitstreams: 1 Torres_DanieleBraz_M.pdf: 2361680 bytes, checksum: 01b222ffefbed9d072457072fb33ccfd (MD5) Previous issue date: 2012 / Resumo: Em países desenvolvidos e em desenvolvimento a desnutrição materno-infantil tem repercussões evidentes sobre a saúde de populações. Isto se deve a alterações no desenvolvimento ontogênico, vinculada à manifestação programada de alterações no desenvolvimento morfológico e funcional de órgãos e sistemas. A programação fetal por desnutrição ou restrição protéica, leva à exposição fetal aumentada aos glicocorticóides maternos e altera a função pós-natal do eixo hipocampo-hipotálamo-pituitária-adrenal podendo ocasionar, no adulto, exposição aumentada cronicamente a glicocorticóides (GC) ou exacerbação na resposta ao estresse. O núcleo da estria terminal (BNST) está localizado em uma posição chave para regular a resposta ao estresse e tem sido implicado no comportamento de ansiedade. Evidências sugerem que esta região cerebral é altamente plástica em termos da morfologia e química neuronal frente a estímulos deletérios...Observação: O resumo, na íntegra, poderá ser visualizado no texto completo da tese digitaL / Abstract: In developed and developing countries maternal and child malnutrition has obvious repercussions on the population health f. This is due to changes in ontogenetic development, linked to the manifestation of programmed changes in morphological and functional development of organs and systems. The fetal programming by malnutrition or protein deficiency leads to increased fetal exposure to maternal glucocorticoids and alters the function of postnatal hippocampal-hypothalamic-pituitary-adrenal axis that may result in chronically increased exposure to glucocorticoids (GC) or exacerbated stress response in adults. The BNST is located in a key position to regulate stress response and has been implicated in anxiety behavior. Evidence suggests that this brain region is highly plastic and responsive to deleterious stimuli in terms of neuronal morphology...Note: The complete abstract is available with the full electronic document / Mestrado / Fisiopatologia Médica / Mestre em Fisiopatologia Médica

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

Abstract Introduction and Background: Methadone, Buprenorphine and other opioid management therapies are being put into effect to help pregnant women who have abused opioids in the months prior to getting pregnant and continued the abuse during pregnancy. Purpose Statement: The purpose of this research was to determine if opioid maintenance therapies would have lasting effects on infants in their growth development. The population in the studies were derived from women who had or were currently abusing opioids during their pregnancy. The interventions taken were to prescribe women with a specific opioid maintenance treatment and measure the outcome on the infant such as birth weight, head circumference, ability to eat, etc. Literature Review: The East Tennessee State University Sherrod Library database was used to search for articles pertaining to the research. The method includes searching for key terms such as opioids on fetal development and ways to improve fetal development with opioid addiction within the years of 2017 to 2022 from peer reviewed journal articles. Findings: The researchers in each study were able to come to a consensus that there were no more effects put into fetal development with the opioid therapy and the subjects that were not given therapy during pregnancy. Conclusion: In the end, some studies showed minor effects that infants would have with getting opioid maintenance therapy in utero but concluded that infants would not experience any more damage to their development by receiving the treatment over infants who did not receive the treatment in utero.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第21650号 / 医博第4456号 / 新制||医||1034(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 大森 孝一, 教授 斎藤 通紀, 教授 戸口田 淳也 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

The objective of this study was to determine breed specific effects of nutritional insults during gestation on regulation of muscle and adipose tissue growth in beef cattle offspring during fetal and early postnatal development. Angus and Brahman heifers were randomly assigned to 1 of 2 dietary treatments consisting of 100% or 60% based on net energy requirements for gestating heifers. Nutritional treatments were imposed from day 50 to 180 of gestation. Fetuses harvested at 180 days of gestation had smaller frames and spared critical organs. Gene expression in several fetal tissues indicated potential for compensatory growth. Postnatally, Brahman offspring weighed less than Angus offspring and had smaller heads and heart girths along with decreased expression of growth and myogenic genes in the Longissimus dorsi. There were no differences in growth or myogenic gene expression within the Longissimus dorsi due to treatment. However, restricted animals had a decreased expression of PPARG.

Yes

BACKGROUND: Various human and animal studies suggest that peak alcohol exposure during a binge episode, rather than total alcohol exposure, may determine fetal development. Research about the impact of binge drinking on birth outcomes is sparse and inconclusive. Data from the Born in Bradford cohort study were used to explore the impact of binge drinking on birth outcomes. METHODS: Interview-administered questionnaire data about the lifestyle and social characteristics of 10 851 pregnancies were linked to maternity and birth data. The impact of self-reported binge drinking (5 units: 40 g of pure alcohol) on two birth outcomes (small for gestational age (SGA) and preterm birth (<37 weeks)) was assessed using multivariate logistic regression models, while adjusting for confounders. RESULTS: The percentage of women classified as binge drinkers fell from 24.5% before pregnancy to 9% during the first trimester and 3.1% during the second trimester. There was a significant association between SGA birth and binge drinking (all categories combined; OR 1.68, 95% CI 1.15 to 2.47, p=0.01). No association was observed between moderate drinking and either birth outcome, or between binge drinking and preterm birth. CONCLUSIONS: Binge drinking during the second trimester of pregnancy was associated with an increased risk of SGA birth. No association was found between any level of alcohol consumption and premature birth. This work supports previous research showing no association between SGA and low-alcohol exposure but adds to evidence of a dose-response relationship with significant risks observed at binge drinking levels.

Background: Previous research suggests that vitamin D deficiency during pregnancy may be associated with suboptimal fetal growth, but direct evidence is lacking. Our objectives were 1) to develop a method for measurement of the fetal sphenoidal fontanelle area (FA) and femur volume (FV) using 3D ultrasound; 2) to create normal charts for FA and FV; and 3) to correlate FA and FV with maternal vitamin D concentration. Methods: FA measurement in 3D was evaluated in vitro and in vivo. Different segmentation methods for FV measurement were explored. A novel FV method was described which consists of three linear measurements and a volume equation; this was validated in vitro and also by comparing FV measured sonographically to the true volume assessed by computed tomography (CT), in 6 cases following pregnancy termination. A cohort of 868 uncomplicated pregnancies was selected on the basis of strict inclusion criteria; participants underwent serial ultrasound scans for FV and multilevel modeling was used for the creation of a “prescriptive” FV chart. Finally, a different cohort of 357 healthy pregnant women had serum vitamin D levels and FV ultrasound at 34 weeks gestation and dual emission x-ray absorptiometry (DEXA) of their neonates in order to investigate the prenatal determinants of fetal bone mass. Results: FA measurement was accurate in vitro, but unreliable in vivo and was therefore abandoned. A novel FV method had excellent agreement with CT and superior repeatability compared with segmentation-based methods. A normal FV chart was created and the regression equations for the median and percentile values were presented. Vitamin D demonstrated a significant correlation with FV. Conclusions: FV is a reliable sonographic marker of skeletal growth. Maternal vitamin D deficiency is associated with reduced FV. This finding has public health implications as reduced bone mass may increase the lifetime risk of osteoporosis, through fetal programming.