No description available.

Por meio desse estudo foi estabelecido um novo modelo de gestação complicada por diabetes tipo 1 em camundongos. O diabetes foi induzido em fêmeas de camundongos Swiss por aloxana e os animais foram acasalados após diferentes períodos de tempo. As fêmeas diabéticas apresentaram hiperglicemia, hipoinsulinemia, glicosúria, polifagia, polidipsia, e diminuição de peso corporal. A histoquímica do Picrosirius demonstrou o aumento dos colágenos fibrilares na decídua do grupo diabético. Análises imunohistoquímicas mostraram aumento dos colágenos I e V e diminuição do colágeno III e dos proteoglicanos biglicam e lumicam. Entretanto, a análise por PCR em tempo real indicou apenas o aumento do mRNA do colágeno I. A microscopia eletrônica revelou alterações na fibrilogênese do colágeno. O miométrio apresentou alterações na organização, citoarquitetura e sistema contráctil das camadas musculares, associadas à diminuição da proliferação celular. Esses resultados contribuem para explicar as alterações no desenvolvimento embrionário e a maior incidência de partos prematuros nas gestações diabéticas. / By means of this study a new mouse model of pregnancy complicated by type 1 diabetes was established. Diabetes was induced in female Swiss mice by alloxan and the animals were mated after different periods of time. Diabetic females showed hyperglycemia, hypoinsulinemia, glycosuria, polyphagy, polydipsy and decreased body weight. Picrosirius histochemistry demonstrated increased fibrillar collagens in the decidua of the diabetic group. Immunohistochemical analysis showed increased collagens I and III, and decreased collagen V and proteoglycans biglycan and lumican. However, real time PCR analysis indicated that only collagen I mRNA was increased. Transmission electron microscopy revealed alterations in collagen fibrillogenesis. The myometrium showed alterations in the organization, cytoarchitecture and contractile system of the muscle layers, associated with decreased proliferation. These results contribute to explain the alterations in embryo development and the higher incidence of preterm labor in diabetic pregnancies.

Diabetic pregnancy is associated with increased risk of congenital malformations. Previous studies have shown that maternal diabetes can interact with the vitamin A metabolite, all-trans retinoic acid (RA), in increasing embryonic susceptibility to caudal regression and neural tube defects. The aim of this thesis is to investigate the cellular and molecular mechanisms that underlie this interaction. / First hypothesis. RA concentration in the embryo is tightly regulated by the synthesizing enzyme retinaldehyde dehydrogenase type II (RALDH2), and the degrading enzyme CYP26. Alteration in expression levels of these enzymes under maternal diabetes may affect the availability of RA and thus its teratogenicity. / In conclusion, results of this thesis provide insight into the mechanism of how maternal diabetes interacts with RA in enhancing embryonic susceptibility to congenital malformations. This is also the first report to show that maternal diabetes alters RA homeostasis. (Abstract shortened by UMI.) / Second hypothesis. The transfer of RA to the nucleus for molecular action is regulated by cytoplasmic cellular retinoic acid binding proteins CRABP-I and CRABP-II. Alteration in expression levels of these binding proteins under maternal diabetes may affect the amount of RA reaching the nucleus and thus its teratogenicity. / Third hypothesis. The action of RA is mediated via different nuclear retinoic acid receptors (RAR) and retinoid X receptors (RXR). Alteration in expression levels of these receptors under maternal diabetes may affect the efficacy of RA signal transduction and thus its teratogenicity. / Three hypotheses are proposed to explain the underlying mechanism of increased embryonic susceptibility to RA teratogenicity under maternal diabetes: / To investigate these hypotheses, expression levels of various genes in different groups were compared. Result show that there are no significant differences in mRNA expression levels of CRABP-I, CRABP-II, RARgamma, RARgamma and RXRalpha between embryos of diabetic and non-diabetic mice with or without RA treatment. In contrast, expression levels of Raldh2 and CYP26 are significantly reduced in embryos of diabetic mothers, and in embryos of non-diabetic mice cultured in vitro in hyperglycemic conditions. Moreover, embryos of diabetic mice show significantly reduced response to RA-induced up-regulation of CYP26. These findings suggest that the rate of degradation of RA is slower in embryos of diabetic mice and thus the teratogenic effect of RA is enhanced. / Leung Bo Wah. / "July 2005." / Adviser: Alisa S. W. Shum. / Source: Dissertation Abstracts International, Volume: 67-07, Section: B, page: 3779. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (p. 158-198). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

Gestational diabetes mellitus (GDM) and infant macrosomia are important obstetric health concerns for Aboriginal populations in Canada. Previous research in non-Aboriginal populations has established that GDM and macrosomia are associated with increased risk of fetal morbidity. Specifically, GDM is a risk factor for infant macrosomia, hypoglycemia, polycythemia, hypocalcemia, and hyperbilirubinemia. Furthermore, macrosomia is an independent risk factor for shoulder dystocia, clavicular fracture, brachial plexus injury, birth asphyxia and operative delivery. The main objectives of this study were to determine prevalence rates of GDM and macrosomia related neonatal complications for the James Bay Cree population of northern Quebec, and to identify risk factors for specific birth trauma injuries and metabolic complications in the population. The prevalence of macrosomia (≥4500 g) was 10.4%, and the estimated prevalence of GDM was 16.6% (95% CI 14.6-18.6) (n = 229/1379). Shoulder dystocia was the most common birth trauma event among the Cree, affecting 2.5% (n = 42/1650) of all Cree births, and 9.3% (n = 16/172) of macrosomic deliveries ≥4500 g. The prevalence of neonatal hypoglycemia was also high, affecting 8.8% (n = 144/1650) of all Cree newborns, and 18.1% (n = 34/192) of GDM deliveries. Macrosomia (BW ≥ 4500 g) was a significant risk factor for shoulder dystocia, clavicular fracture, hypoglycemia, and caesarean section delivery. After adjusting for maternal age, parity, and gestational age, GDM was identified as a significant risk factor for macrosomia (≥4500 g), hypoglycemia, polycythemia, and hypocalcemia. In summary, this study identified a high incidence of neonatal complications among the James Bay Cree compared with rates in the general North American population. These outcomes can be explained, in part, by high prevalence rates of gestational diabetes and infant macrosomia. Further studies to investigate the long-term consequences of GDM and

Por meio desse estudo foi estabelecido um novo modelo de gestação complicada por diabetes tipo 1 em camundongos. O diabetes foi induzido em fêmeas de camundongos Swiss por aloxana e os animais foram acasalados após diferentes períodos de tempo. As fêmeas diabéticas apresentaram hiperglicemia, hipoinsulinemia, glicosúria, polifagia, polidipsia, e diminuição de peso corporal. A histoquímica do Picrosirius demonstrou o aumento dos colágenos fibrilares na decídua do grupo diabético. Análises imunohistoquímicas mostraram aumento dos colágenos I e V e diminuição do colágeno III e dos proteoglicanos biglicam e lumicam. Entretanto, a análise por PCR em tempo real indicou apenas o aumento do mRNA do colágeno I. A microscopia eletrônica revelou alterações na fibrilogênese do colágeno. O miométrio apresentou alterações na organização, citoarquitetura e sistema contráctil das camadas musculares, associadas à diminuição da proliferação celular. Esses resultados contribuem para explicar as alterações no desenvolvimento embrionário e a maior incidência de partos prematuros nas gestações diabéticas. / By means of this study a new mouse model of pregnancy complicated by type 1 diabetes was established. Diabetes was induced in female Swiss mice by alloxan and the animals were mated after different periods of time. Diabetic females showed hyperglycemia, hypoinsulinemia, glycosuria, polyphagy, polydipsy and decreased body weight. Picrosirius histochemistry demonstrated increased fibrillar collagens in the decidua of the diabetic group. Immunohistochemical analysis showed increased collagens I and III, and decreased collagen V and proteoglycans biglycan and lumican. However, real time PCR analysis indicated that only collagen I mRNA was increased. Transmission electron microscopy revealed alterations in collagen fibrillogenesis. The myometrium showed alterations in the organization, cytoarchitecture and contractile system of the muscle layers, associated with decreased proliferation. These results contribute to explain the alterations in embryo development and the higher incidence of preterm labor in diabetic pregnancies.

No description available.

<p>Women with pregestational diabetes have a 2-5 fold increased risk of giving birth to malformed babies compared with non-diabetic women. Diabetes-induced oxidative stress in maternal and embryonic tissues has been implicated in the teratogenic process. The malformations are likely to be induced before the seventh week of pregnancy, when the yolk sac is partly responsible for the transfer of metabolites to the embryo, and the uterine blood flow to the implantation site determines the net amount of nutrients available to the conceptus. We aimed to evaluate the effect on embryogenesis caused by a diabetes-induced disturbance in yolk sac morphology, uterine blood flow or altered maternal antioxidative status in conjunction with a varied severity of the maternal diabetic state.</p><p>We investigated to which extent maternal diabetes with or without folic acid (FA) supplementation affects mRNA levels and protein distribution of ROS scavenging enzymes (SOD, CAT, GPX), vascular endothelial growth factor-A (Vegf-A), folate binding protein-1 (Folbp-1), and apoptosis associated proteins (Bax, Bcl-2, Caspase-3) in the yolk sacs of rat embryos on gestational days 10 and 11. We found that maternal diabetes impairs, and that FA supplementation restores, yolk sac vessel morphology, and that maternal diabetes is associated with increased apoptotic rate in embryos and yolk sacs, as well as impaired SOD gene expression. We assessed uterine blood flow with a laser-Doppler-flow-meter and found increased blood flow to implantation sites of diabetic rats compared with controls. Furthermore, resorbed and malformed offspring showed increased and decreased blood flow to their implantation sites, respectively. In mice with genetically altered CuZnSOD levels, maternal diabetes increased embryonic dysmorphogenesis irrespective of CuZnSOD expression. We thus found the maternal diabetic state to be a major determinant of diabetic embryopathy and that the CuZnSOD status exerts a partial protection for the embryo in diabetic pregnancy. </p>

Introdução e objetivos – A finalidade prioritária no tratamento do diabetes mellitus gestacional (DMG) é alcançar níveis de glicemia materna tão próximos da normalidade quanto possível, a fim de reduzir os efeitos adversos associados à hiperglicemia na gestação. A auto verificação da glicemia capilar (perfil glicêmico) é o método mais usado para a monitorização do controle metabólico na gestação complicada por diabetes. Nosso objetivo foi analisar as associações entre os perfis glicêmicos maternos com os principais desfechos da gestação numa população de mulheres com DMG acompanhadas em ambulatório de pré-natal especializado em hospital universitário no sul do Brasil, Hospital de Clínicas de Porto Alegre (HCPA). Desenho e metodotologia – conduzimos um estudo de coorte prospectiva de gestantes referidas da rede de atenção primária de saúde pública para tratamento do DMG no HCPA, acompanhadas do diagnóstico ao parto. Pesquisamos associações entre os resultados dos perfis glicêmicos com o peso de nascimento e com o risco de recém-nascidos grandes para idade gestacional e de desfechos adversos perinatais. Resultados – acompanhamos 440 mulheres com DMG. A média do índice de massa corporal (IMC) foi 33.3kg/m2. 351 bebês (79.8%) mostraram peso adequado à idade gestacional no nascimento. As médias de glicemia nos perfis pré e pósprandiais aumentaram com o avanço na categoria de peso nascimento. Três ou mais perfis glicêmicos anormais foram o fator de risco mais robusto para o nascimento de bebês grandes (OR 3.15 1.51-6.55) e para o desenvolvimento de desfechos adversos perinatais (OR 2.28 1.59-3.29). O ganho de peso materno durante o tratamento associou-se ao risco de recém-nascido grande para idade gestacional, assim como o IMC pré-gestacional, esse último também fator de risco independente para eventos perinatais adversos. Conclusão – perfis glicêmicos anormais em mais de 2 ocasiões foram o fator de risco mais relacionado ao nascimento de um bebê grande para a idade gestacional e para o desenvolvimento de complicações neonatais. Efeito benéfico do tratamento do DMG, guiado pelos perfis glicêmicos, foi a maioria de recém-nascidos com peso adequado à idade gestacional nessa coorte, apesar da incidência de desfechos perinatais adversos não ter sido diferente entre as categorias de peso fetal de nascimento. / Background and objective – a priority target in the treatment of gestational diabetes mellitus (GDM) is attaining maternal glucose levels as close as possible to euglycemia, in order to decrease the adverse outcomes linked to hyperglycemia. Self-performed capillary glucose (glycemic profile) is the most widely used method for metabolic monitoring in pregnancy complicated by diabetes. We intended to analyze the associations of maternal glycemic profile to main pregnancy outcomes in a population of GDM women treated in a specialized prenatal clinic at a university hospital in South Brazil, Hospital de Clínicas de Porto Alegre (HCPA). Research design and methodology – we conducted a prospective cohort study of pregnant women, referred from public primary health care for treatment of GDM at HCPA, between 2008 and 2015. We searched associations of glycemic profiles to birth weight, large for gestational age newborn and adverse neonatal outcomes. Results – we followed 440 GDM women from diagnosis to delivery. Mean prepregnancy body mass index (BMI) was 33.3kg/m2; 351 babies (79.8%) had appropriate birth weight for gestational age. Mean glucose in pre-prandial and postprandial profiles increased with raising birth weight category. Three or more abnormal glycemic profiles showed the strongest association to a large baby (OR 3.15 1.51-6.55) and to a composite of adverse neonatal outcomes (OR 2.28 1.59- 3.29). Gestational weight gain in the course of treatment was associated to large babies, as pre-pregnancy BMI, the latter also an independent risk factor for adverse neonatal outcome. Conclusion – abnormal maternal glycemic profiles in more than two occasions were the stronger risk factor for delivering a large baby and for developing neonatal complications. A beneficial effect of GDM treatment, guided by glycemic profiles, was that most of our newborns had birth weight appropriate for gestational age, although incidence of adverse neonatal outcomes had been no different across birth weight categories.

Women with pregestational diabetes have a 2-5 fold increased risk of giving birth to malformed babies compared with non-diabetic women. Diabetes-induced oxidative stress in maternal and embryonic tissues has been implicated in the teratogenic process. The malformations are likely to be induced before the seventh week of pregnancy, when the yolk sac is partly responsible for the transfer of metabolites to the embryo, and the uterine blood flow to the implantation site determines the net amount of nutrients available to the conceptus. We aimed to evaluate the effect on embryogenesis caused by a diabetes-induced disturbance in yolk sac morphology, uterine blood flow or altered maternal antioxidative status in conjunction with a varied severity of the maternal diabetic state. We investigated to which extent maternal diabetes with or without folic acid (FA) supplementation affects mRNA levels and protein distribution of ROS scavenging enzymes (SOD, CAT, GPX), vascular endothelial growth factor-A (Vegf-A), folate binding protein-1 (Folbp-1), and apoptosis associated proteins (Bax, Bcl-2, Caspase-3) in the yolk sacs of rat embryos on gestational days 10 and 11. We found that maternal diabetes impairs, and that FA supplementation restores, yolk sac vessel morphology, and that maternal diabetes is associated with increased apoptotic rate in embryos and yolk sacs, as well as impaired SOD gene expression. We assessed uterine blood flow with a laser-Doppler-flow-meter and found increased blood flow to implantation sites of diabetic rats compared with controls. Furthermore, resorbed and malformed offspring showed increased and decreased blood flow to their implantation sites, respectively. In mice with genetically altered CuZnSOD levels, maternal diabetes increased embryonic dysmorphogenesis irrespective of CuZnSOD expression. We thus found the maternal diabetic state to be a major determinant of diabetic embryopathy and that the CuZnSOD status exerts a partial protection for the embryo in diabetic pregnancy.

Introdução e objetivos – A finalidade prioritária no tratamento do diabetes mellitus gestacional (DMG) é alcançar níveis de glicemia materna tão próximos da normalidade quanto possível, a fim de reduzir os efeitos adversos associados à hiperglicemia na gestação. A auto verificação da glicemia capilar (perfil glicêmico) é o método mais usado para a monitorização do controle metabólico na gestação complicada por diabetes. Nosso objetivo foi analisar as associações entre os perfis glicêmicos maternos com os principais desfechos da gestação numa população de mulheres com DMG acompanhadas em ambulatório de pré-natal especializado em hospital universitário no sul do Brasil, Hospital de Clínicas de Porto Alegre (HCPA). Desenho e metodotologia – conduzimos um estudo de coorte prospectiva de gestantes referidas da rede de atenção primária de saúde pública para tratamento do DMG no HCPA, acompanhadas do diagnóstico ao parto. Pesquisamos associações entre os resultados dos perfis glicêmicos com o peso de nascimento e com o risco de recém-nascidos grandes para idade gestacional e de desfechos adversos perinatais. Resultados – acompanhamos 440 mulheres com DMG. A média do índice de massa corporal (IMC) foi 33.3kg/m2. 351 bebês (79.8%) mostraram peso adequado à idade gestacional no nascimento. As médias de glicemia nos perfis pré e pósprandiais aumentaram com o avanço na categoria de peso nascimento. Três ou mais perfis glicêmicos anormais foram o fator de risco mais robusto para o nascimento de bebês grandes (OR 3.15 1.51-6.55) e para o desenvolvimento de desfechos adversos perinatais (OR 2.28 1.59-3.29). O ganho de peso materno durante o tratamento associou-se ao risco de recém-nascido grande para idade gestacional, assim como o IMC pré-gestacional, esse último também fator de risco independente para eventos perinatais adversos. Conclusão – perfis glicêmicos anormais em mais de 2 ocasiões foram o fator de risco mais relacionado ao nascimento de um bebê grande para a idade gestacional e para o desenvolvimento de complicações neonatais. Efeito benéfico do tratamento do DMG, guiado pelos perfis glicêmicos, foi a maioria de recém-nascidos com peso adequado à idade gestacional nessa coorte, apesar da incidência de desfechos perinatais adversos não ter sido diferente entre as categorias de peso fetal de nascimento. / Background and objective – a priority target in the treatment of gestational diabetes mellitus (GDM) is attaining maternal glucose levels as close as possible to euglycemia, in order to decrease the adverse outcomes linked to hyperglycemia. Self-performed capillary glucose (glycemic profile) is the most widely used method for metabolic monitoring in pregnancy complicated by diabetes. We intended to analyze the associations of maternal glycemic profile to main pregnancy outcomes in a population of GDM women treated in a specialized prenatal clinic at a university hospital in South Brazil, Hospital de Clínicas de Porto Alegre (HCPA). Research design and methodology – we conducted a prospective cohort study of pregnant women, referred from public primary health care for treatment of GDM at HCPA, between 2008 and 2015. We searched associations of glycemic profiles to birth weight, large for gestational age newborn and adverse neonatal outcomes. Results – we followed 440 GDM women from diagnosis to delivery. Mean prepregnancy body mass index (BMI) was 33.3kg/m2; 351 babies (79.8%) had appropriate birth weight for gestational age. Mean glucose in pre-prandial and postprandial profiles increased with raising birth weight category. Three or more abnormal glycemic profiles showed the strongest association to a large baby (OR 3.15 1.51-6.55) and to a composite of adverse neonatal outcomes (OR 2.28 1.59- 3.29). Gestational weight gain in the course of treatment was associated to large babies, as pre-pregnancy BMI, the latter also an independent risk factor for adverse neonatal outcome. Conclusion – abnormal maternal glycemic profiles in more than two occasions were the stronger risk factor for delivering a large baby and for developing neonatal complications. A beneficial effect of GDM treatment, guided by glycemic profiles, was that most of our newborns had birth weight appropriate for gestational age, although incidence of adverse neonatal outcomes had been no different across birth weight categories.