by Pui-Kwong Chan. / Thesis -- The Chinese University of Hong Kong. / Bibliography: leaves 139-145.

Kwok-pui Fung. / Thesis (M.Ph.)--Chinese University of Hong Kong, 1975. / Bibliography: leaves 122-131.

Thesis (M.Ph.)--Chinese University of Hong Kong. / Bibliography: leaves 87-96.

Pre-eclampsia, often described as toxaemia of pregnancy, historically represents one of the most widely investigated conditions relating to human reproduction. To date no firm cure has been found and a clear, well defined mechanism has not been ascribed to the pathogenesis of the disease. Researchers seem to focus on single pathways in isolation of others. The disease rather represents a multitude of possible underlying pathologies nvolving genetics, immune dysregulation, vascular maladaptation, and sociobiological factors thus complicating the approach to treatment. However, a central theme is the presence of reduced placental perfusion resulting in a hypoxic and/or ischaemic placenta and the subsequent secretion of various factors that initiate the maternal syndrome. It is within this context that we examine how an intervention such as increasing placental perfusion may represent a promising treatment strategy for this disease. We sought to manipulate the vasodilatory mechanisms of the uterine vasculature using sildenafil citrate and a flavonoid extracted from Eriosema kraussianum (Kr2), in Sprague-Dawley rats that exhibited preeclampsia-like manifestations. Both treatment regimens improved fetal outcomes and reduced blood pressure amplification and proteinuria. They also reduced the plasma concentrations of the two anti-angiogenic factors; sFlt1 and sEng. Only sildenafil citrate improved nitric oxide levels which was expected, suggesting that Kr2 causes vasodilation by some other mechanism. Nevertheless, both compounds improved both pup and placental weights, suggesting that they also improve utero-placental perfusion. These findings that selective uterine vascular dilation improves placental perfusion may be promising in averting possible death to mothers and their babies from pre-eclampsia especially in low resource environments. / Thesis (Ph.D.)-University of KwaZulu-Natal, Westville, 2011.

Adequate maternal, intervillous and fetal blood flow are all necessary for fetal wellbeing. Compromise to any part of this exchange would be detrimental to pregnancy outcome. Preeclampsia is associated with reduced maternal spiral artery flow, resulting in reduced placental perfusion. This in turn creates an ischemic environment which may pre-dispose morphological changes in placental villi. This pilot study utilized morphometric image analysis to examine some features of the fetal component of the placenta in normotensive (NT) and pre-eclamptic (PE) groups. The features examined included: density of placental villi (expressed as percentage of field area occupied by placental tissue); stem vessel carrying capacity (expressed as percentage of stem villus area occupied by vessel lumina); the thickness of the stem arterial walls relative to artery size (expressed as percentage of artery area occupied by arterial wall) and the extent of fibrosis associated with villi (expressed as percentage of field area occupied by fibrosis). The results were as follows: density of placental villus arrangement NT:51.89±6.19, PE:64.78±6.93 (P<0.001); carrying capacity of stem villi NT:17.20±11.78, PE:8.67±8.51 (P<0.001); relative thickness of stem villi arterial walls NT:74.08±12.92, PE: 86.85±10.55 (P<0.001); and extent of fibrosis NT:0.727±0.310, PE:1.582±0.707 (P<0.001). These significant differences between normotensive and pre-eclamptic placentae suggest possible fetal maladaptations in response to the intervillous ischemia, compounding the existing maternal compromise to materno-fetal exchange. / Thesis (M.Med.)-University of KwaZulu-Natal, Durban, 2012.

Facultat de Medicina. Universidad Centrall. 1897 / "Una de las peores complicaciones que pueden presentarse, ya en el transcurso del embarazo, ya durante el parto; es, sin ningún género de duda la denominada “placenta praevia”, ó sea la inserción de ésta en el segmento inferior del útero; dando ella lugar á silenciosas hemórragias, que debutando de una .manera insidiosa en la generalidad de los casos y en el transcurso de los tres últimos meses, producen tan funestos resultados, que según estadísticas de la primera mitad de nuestro' siglo (33% de mortalidad materna y 67% de mortalidad infantil), hicieron que con razón Simpson las incluyera entre las epidemias más mortíferas y que Noegele las contara entre los errores más funestos de la naturaleza". "No es extraño, pues, que dada la importancia del asunto, haya sido objeto de innumerables trabajos y que haya preocupado y preocupe aún el ánimo de los más eminentes tocólogos, dando ello origen á multitud de teorías para explicar dichas hemorragias y como derivado de ellas diversos métodos para su tratamiento, cuyos resultados y digámoslo como á gloria á la eterna memoria de tan ilustres héroes de la ciencia, son tan satisfactorios hoy día, que nos permiten salvar gran número de vidas, en otro tiempo condenadas á extinguirse, por falta de medios y de conocimientos exactos sobre tal complicación." "¿A cual de entre tantas teorías como han venido emitiéndose debemos hoy día dar la preferencia?” “¿Y qué procedimiento reune el mayor número de ventajas, ya para la madre ya para el infante? Cuestión es ésta, bastante debatida hoy día y lejos de estar resuelta, pues cuando consultamos los autores clásicos, vemos reinar en ellos apasionamientos, ya para el uno ya para otro método, siéndonos algo difícil encontrar uno, que estudie el asunto, con la suficiente imparcialidad, para marcarnos la linea, de conducta bien trillada para tales casos.”' “Al escojer, pues, como sujeto, de nuestra memoria tan árduo asunto, no se crea que tengamos ni remotamente la pretensión de zanjar lo que hombres de tanto valer como los que hoy se encuentran al frente de la Tocología no han hecho; sino solamente emitir una opinión, que al lado de muchas otras resultará la menos valedera de todas, ciertamente, pero al sustentarla dentro de la medida de nuestras escasas fuerzas, procuraremos que sea con 'la mayor imparcialidad posible.” “Para ello dividiremos nuestro modesto trabajo en dos partes: objeto de la primera será una breve reseña histórica de lo que ha venido haciéndose desde tiempos antiguos y guardaremos para la segunda un ligero estudio crítico de las diversas teorías y procedimientos que hoy día se usan, escogiendo el que según nuestro parecer sea de más fácil y sencilla aplicación, reuna más ventajas y mejores datos estadísticos aporte en su favor”.

Pregnancy complications associated with placental development affect approximately one third of all human pregnancies. Genome health is essential for placental and fetal development, as DNA damage can lead to pregnancy loss and developmental defects. During this developmental phase rapid DNA replication provides an increased opportunity for genome and epigenome damage to occur[1]. Maternal nutrition is one of the principal environmental factors supporting the high rate of cell proliferation and differentiation. Folate functions in one-carbon metabolism and regulates DNA synthesis, DNA repair and gene expression[1]. Deficiencies or defects in gene-nutrient interactions associated with one-carbon metabolism can lead to inhibition of cell division, cell cycle delay and an excessive apoptotic or necrotic cell death rate [2], which may affect placentation. This study is the first to investigate the association between genomic damage biomarkers in late pregnancy complications associated with uteroplacental insufficiency (UPI) including preeclampsia and intrauterine growth restriction (IUGR). The results indicate that genome damage in the form of micronucleated cells in peripheral blood lymphocytes at 20 weeks gestation is significantly increased in women at risk of developing an adverse pregnancy outcome. The observed OR for the high micronuclei frequency may be the highest observed for any biomarker selected in relation to risk of pregnancy complications to date (15.6 – 33.0). In addition, reduced apoptosis was observed in association with increased micronuclei, suggesting that the cells may have escaped specific cell-cycle checkpoints allowing a cell with DNA damage to proceed through mitosis. This study demonstrated that an increase in plasma homocysteine concentration at 20 weeks gestation is associated prospectively with the subsequent development of UPI, indicating a causal relationship. The MTR 2756 GG genotype was significantly associated with increased plasma homocysteine concentration and UPI. Furthermore, the MTHFD1 1958 single nucleotide polymorphism was associated with increased risk for IUGR. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1309296 / Thesis (Ph.D.) -- School of Paediatrics and Reproductive Health, 2007

Pregnancy complications associated with placental development affect approximately one third of all human pregnancies. Genome health is essential for placental and fetal development, as DNA damage can lead to pregnancy loss and developmental defects. During this developmental phase rapid DNA replication provides an increased opportunity for genome and epigenome damage to occur[1]. Maternal nutrition is one of the principal environmental factors supporting the high rate of cell proliferation and differentiation. Folate functions in one-carbon metabolism and regulates DNA synthesis, DNA repair and gene expression[1]. Deficiencies or defects in gene-nutrient interactions associated with one-carbon metabolism can lead to inhibition of cell division, cell cycle delay and an excessive apoptotic or necrotic cell death rate [2], which may affect placentation. This study is the first to investigate the association between genomic damage biomarkers in late pregnancy complications associated with uteroplacental insufficiency (UPI) including preeclampsia and intrauterine growth restriction (IUGR). The results indicate that genome damage in the form of micronucleated cells in peripheral blood lymphocytes at 20 weeks gestation is significantly increased in women at risk of developing an adverse pregnancy outcome. The observed OR for the high micronuclei frequency may be the highest observed for any biomarker selected in relation to risk of pregnancy complications to date (15.6 – 33.0). In addition, reduced apoptosis was observed in association with increased micronuclei, suggesting that the cells may have escaped specific cell-cycle checkpoints allowing a cell with DNA damage to proceed through mitosis. This study demonstrated that an increase in plasma homocysteine concentration at 20 weeks gestation is associated prospectively with the subsequent development of UPI, indicating a causal relationship. The MTR 2756 GG genotype was significantly associated with increased plasma homocysteine concentration and UPI. Furthermore, the MTHFD1 1958 single nucleotide polymorphism was associated with increased risk for IUGR. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1309296 / Thesis (Ph.D.) -- School of Paediatrics and Reproductive Health, 2007

Intrauterine infection with the oral commensal anaerobe Fusobacterium nucleatum has been associated with adverse pregnancy outcomes. We have previously established a mouse model to study the mechanism of hematogenous F. nucleatum leading to fetal and neonatal death. Here, we report that Toll-like Receptor 4 (TLR4) from the maternal rather than paternal, and endothelial rather than hematopoietic cells mediate placental inflammation, especially the production of the proinflammatory cytokine interleukin-1 beta. Downstream of TLR4, a spatiotemporal pattern of the transcription factor NF-kB activation was observed spreading from the decidual endothelium to the surrounding spongiotrophoblasts within the first six hours of infection. Maternal TRIF, an adaptor protein downstream of TLR4 pathway, but not NLRP3, a cytosolic signaling receptor that constitutes inflammasome complex, mediated the fetal and neonatal death. In an effort to find a prophylactic preventive method against the detrimental birth outcome induced by F. nucleatum placental infection, omega-3 fatty acids were tested for their anti-inflammatory properties. Omega-3 oil supplementation in pregnant mice inhibited the transcription and release of inflammatory cytokines, prevented fetal and neonatal death, and also suppressed the proliferation of F. nucleatum in the placenta. Moreover, omega-3 supplementation was shown to enhance neutrophil recruitment to the site of infection. However, omega-3 supplementation did not protect the pregnancy from Listeria monocytogenes infection in vivo, despite the in vitro results where inflammation induced by both Gram-negative and Gram-positive bacteria were suppressed by omega-3 fatty acids. This study presents the first direct evidence of maternal, rather than fetal, signal leading to adverse pregnancy outcome, and suggests an exciting therapeutic potential of dietary omega-3 fatty acids.

Thesis (Ph. D.)--University of Washington, 2006. / Vita. Includes bibliographical references (leaves 85-102).