This thesis reports the effects of an altered intrauterine environment on the offspring???s renal, cardiovascular and renin angiotensin systems. After a midgestational asphyxial episode in fetal sheep (30 min total umbilical cord occlusion at 90 days; term 150 days) the hydrops that resulted had not completely resolved by 130 days. While the heart and kidneys were apparently unaffected, the brain and lung weights were 37% and 50% lower than sham values, respectively and there were joint contractures. The effects of maternal renal disease on the offspring were investigated. Although in utero fetuses of subtotally nephrectomised ewes (STNx) had altered urine flow rates, sodium excretion, haematocrits, plasma chloride and plasma renin levels, by 1-2 weeks after birth these values in the lambs (STNxL) were similar to controls (ConL) under baseline conditions. Body weight and the weights of most organs were similar, including the kidney, in which glomerular number was normal. In the neonatal period, the lambs were subjected to four challenges: furosemide (2 mg/kg intravenous bolus), infusion of angiotensin II and phenylephrine, intravenous infusion of 0.15M saline (50 ml/kg over 30 min) and haemorrhage (20% estimated blood volume over 10 min). These challenges revealed evidence of programming of several aspects of the renal, cardiovascular and renin angiotensin systems in the STNx offspring. As young adults at 6 months of age, male and female offspring of STNx ewes were normotensive and had normal renal function. On a high salt diet (HSD, 0.17M NaCl in 8L water for 5-7days), female offspring of both groups did not become hypertensive. However, the STNx offspring must have retained salt and water as plasma sodium was increased and haematocrit was decreased. In the STNx offspring only, there was a relationship between glomerular filtration rate (GFR) and mean arterial pressure, indicating an inability to maintain a constant GFR in response to changes in arterial pressure.

Intrauterine Growth Restriction (IUGR) is evident in infants born with a reduced weight or length, and/or increased thinness for gestational age. IUGR is associated with altered postnatal growth and regulation, due to unknown mechanisms. Much clinical IUGR results from the reduced delivery of essential substrates (oxygen and nutrients) to the fetus, due to either maternal or placental limitations. Catch-up growth (accelerated rate of growth in absolute or fractional terms) occurs in the majority of IUGR infants, and returns an infant to their predetermined growth curve. IUGR is associated with increased risks of morbidity and mortality in the perinatal period, and with a reduced final adult stature and increased risk of adult onset diseases, particularly diabetes and cardiovascular disease. Catch-up growth after IUGR predicts improved health in terms of reduced hospital visits in infants and children, and an increased final adult stature but also predicts an increased risk of developing obesity, as well as diabetes and cardiovascular disease. The underlying mechanisms for catch-up growth may contribute to this range of outcomes in later life, but are poorly understood. Studies in IUGR infants have demonstrated increased absolute and/or fractional growth rates following birth, termed catch-up growth, in the presence of reduced or normal plasma concentrations of the thyroid hormones and major anabolic hormones (insulin and/or IGF-I). This suggests that increased sensitivity to, rather than increased production of insulin, IGF-I and thyroid hormone, causes catch-up growth following IUGR. We therefore hypothesised that placental restriction of fetal growth would reduce size at birth and increase postnatal growth and adiposity in association with increased metabolic sensitivity to insulin, IGFs and thyroid hormones. This study has shown that the placentally restricted (PR) lamb has a reduced size at birth in terms of soft and skeletal tissues, has increased rates of growth postnatally, and has increased adiposity by six weeks of age. We have also shown that PR of fetal growth in the sheep did not alter gestational age at delivery, but reduced survival rate. PR lambs demonstrated catch-up growth in most parameters by 30 days of age and increased adiposity at six weeks of age compared to the control lambs. Placental restriction increased insulin and IGF sensitivity of circulating free fatty acids, which in turn, predicts increased adiposity. Neonatal catch-up growth after fetal growth restriction was substantially predicted by both abundance of, and metabolic sensitivity to insulin, suggesting increased insulin action as an underlying cause. Catch-up growth occurs in the neonate despite reduced concentrations of fasting plasma IGFs, along with increased IGF sensitivity of free fatty acid metabolism and adiposity. Plasma TH concentrations predicted growth of soft and skeletal tissue in lambs during early postnatal life, particularly in those undergoing catch-up growth following PR. Therefore neonatal catch-up growth after IUGR is associated with increased sensitivity to both insulin and IGFs, particularly of circulating free fatty acids, and appears to occur to the extent allowed by the prevailing abundance of these hormones and of thyroid hormones. If this altered endocrine state persists, increased adiposity and its subsequent amplification may contribute to the development of obesity, and related adverse metabolic and cardiovascular outcomes in adult life. / Thesis (Ph.D.)--School of Molecular and Biomedical Science, 2004.

Bibliography: leaves 284-298 / 4 microfiches (339 fr.) : / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Summary: Shows that foetal acidosis is related to prolongation of the QT interval, a change which cannot be accounted for in foetal heart rate. Describes the configuration and time constants of the foetal electrocardiogram both during labour and at the time of delivery in normal and acidotic subjects. Confirms that foetal acidosis during labour is associated with acidosis at the time of delivery and with clinical depression of the newborn infant / Thesis (M.D.)--Dept. of Obstetrics and Gynaecology, University of Adelaide, 1970

Bibliography: leaves [11-1]-11-19 / 1 v. (various pagings) : ill ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, 1987

"March 2003" / Includes bibliographical references (leaves 237-297) / ix, 297 leaves : ill. (some col.), plates (col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, School of Agriculture and Wine, Discipline of Animal Science, 2005

This thesis reports the effects of an altered intrauterine environment on the offspring???s renal, cardiovascular and renin angiotensin systems. After a midgestational asphyxial episode in fetal sheep (30 min total umbilical cord occlusion at 90 days; term 150 days) the hydrops that resulted had not completely resolved by 130 days. While the heart and kidneys were apparently unaffected, the brain and lung weights were 37% and 50% lower than sham values, respectively and there were joint contractures. The effects of maternal renal disease on the offspring were investigated. Although in utero fetuses of subtotally nephrectomised ewes (STNx) had altered urine flow rates, sodium excretion, haematocrits, plasma chloride and plasma renin levels, by 1-2 weeks after birth these values in the lambs (STNxL) were similar to controls (ConL) under baseline conditions. Body weight and the weights of most organs were similar, including the kidney, in which glomerular number was normal. In the neonatal period, the lambs were subjected to four challenges: furosemide (2 mg/kg intravenous bolus), infusion of angiotensin II and phenylephrine, intravenous infusion of 0.15M saline (50 ml/kg over 30 min) and haemorrhage (20% estimated blood volume over 10 min). These challenges revealed evidence of programming of several aspects of the renal, cardiovascular and renin angiotensin systems in the STNx offspring. As young adults at 6 months of age, male and female offspring of STNx ewes were normotensive and had normal renal function. On a high salt diet (HSD, 0.17M NaCl in 8L water for 5-7days), female offspring of both groups did not become hypertensive. However, the STNx offspring must have retained salt and water as plasma sodium was increased and haematocrit was decreased. In the STNx offspring only, there was a relationship between glomerular filtration rate (GFR) and mean arterial pressure, indicating an inability to maintain a constant GFR in response to changes in arterial pressure.

This thesis reports the effects of an altered intrauterine environment on the offspring???s renal, cardiovascular and renin angiotensin systems. After a midgestational asphyxial episode in fetal sheep (30 min total umbilical cord occlusion at 90 days; term 150 days) the hydrops that resulted had not completely resolved by 130 days. While the heart and kidneys were apparently unaffected, the brain and lung weights were 37% and 50% lower than sham values, respectively and there were joint contractures. The effects of maternal renal disease on the offspring were investigated. Although in utero fetuses of subtotally nephrectomised ewes (STNx) had altered urine flow rates, sodium excretion, haematocrits, plasma chloride and plasma renin levels, by 1-2 weeks after birth these values in the lambs (STNxL) were similar to controls (ConL) under baseline conditions. Body weight and the weights of most organs were similar, including the kidney, in which glomerular number was normal. In the neonatal period, the lambs were subjected to four challenges: furosemide (2 mg/kg intravenous bolus), infusion of angiotensin II and phenylephrine, intravenous infusion of 0.15M saline (50 ml/kg over 30 min) and haemorrhage (20% estimated blood volume over 10 min). These challenges revealed evidence of programming of several aspects of the renal, cardiovascular and renin angiotensin systems in the STNx offspring. As young adults at 6 months of age, male and female offspring of STNx ewes were normotensive and had normal renal function. On a high salt diet (HSD, 0.17M NaCl in 8L water for 5-7days), female offspring of both groups did not become hypertensive. However, the STNx offspring must have retained salt and water as plasma sodium was increased and haematocrit was decreased. In the STNx offspring only, there was a relationship between glomerular filtration rate (GFR) and mean arterial pressure, indicating an inability to maintain a constant GFR in response to changes in arterial pressure.

<p>The modern world is facing a revolutionary development in the clinical medicine and biomedical sciences. Due to the different life supporting systems, it is easily possible to keep patients with severe diseases alive. With organ transplantation a lot of people, who would otherwise die can live long and happy lives. In vitro fertilization allows a woman to bear the child that is not genetically related to her. Due to the possibility of contraception, safe abortions and prenatal diagnosis, women and couples can make preferable choices concerning their future child. Such medical developments and improvements have a great impact on our life, and provoke a lot of ethical questions and moral dilemmas.</p><p>The aim of this thesis is to answer the question whether prenatal diagnosis can be justified as it mainly leads to the selective abortion, whether and when the fetus counts as a person and whether the prospective parents can perform selective abortion on the basis of fetal disability; and to discuss ethical problems that are experienced by the doctor, who brings the news into the family and what is his/her role in the decision-making process.</p>

<p>Chicken fetuses exposed to chronic hypoxia suffer from growth retardation and</p><p>induces an overall sympathetic activity, including elevation of the concentration</p><p>of circulating catecholamines. Simultaneously, hypoxic fetuses display a</p><p>lowered β-adrenoreceptor (βAR) density in myocardial tissue. In vertebrates,</p><p>β1AR and β2AR are the most important signalling pathways for acute elevation</p><p>of cardiac performance. The aim of this study was to see how chronic hypoxia</p><p>affects the level of messenger RNA (mRNA) for the β1AR in the fetal chicken</p><p>heart at different developmental ages. The broiler chicken is a suitable model</p><p>organism for studying the progression of heart failure because the fast growth</p><p>rate requires a large increase in blood perfusion at the end of fetal development.</p><p>The β1AR sequence of the broiler chicken is 1587 bp and located on</p><p>chromosome 6. When running a PCR for quantification of the sequence,</p><p>primers for almost the whole sequence failed (1404 bp) and so did primers of</p><p>1193 bp; instead primers of 692 bp of the sequence were used and made</p><p>quantification possible. Similar results were obtained from both the heart and</p><p>liver of day 15 fetal chickens. The PCR product was cloned into a TOPO vector</p><p>and sent for sequencing, to enable the making of a probe for a northern blot</p><p>analysis of the mRNA in the fetal chicken hearts.</p>

Lymphomas and leukemias are the most common cancer in children and young adults and in utero exposure to carcinogens may contribute to the etiology of these cancers. A polycyclic aromatic hydrocarbon (PAH), dibenzo[a,l]pyrene (DBP), was administered to pregnant mice (15 mg/Kg b.w., gavage) on gestation day 17. Significant mortalities in young offspring were observed due to T-cell lymphoma. Lung and liver tumors also were observed in survivors at 10 months of age. To assess the role of the Aryl Hydrocarbon Receptor (AHR), we utilized crosses of B6129SF1/J (responsive) mice with strain 129S1/SvImJ (non-responsive). Offspring born to AHR non-responsive mothers had greater susceptibility to lymphoma, irrespective of offspring genotype. Responsive offspring displayed increased mortality if the mother was responsive. Lung adenomas showed Ki-ras mutations and exhibited a 50% decrease and a 35-fold increase in expression of Rb and p19/ARF mRNA, respectively. To examine the risk/benefit of maternal dietary phytochemical treatment against transplacental cancer, 2000 ppm indole-3-carbinol (I3C) was given to pregnant mice through diet from gestation day 9 till weaning. I3C significantly lowered mortality caused by lymphomas regardless of the maternal genotype, and also reduced lung tumor multiplicity in offspring born to AHR [superscript b-l/d] dams. Distribution of I3C in most maternal and fetal tissues was quantified following a single gavage of [¹⁴C]-I3C to the pregnant mice. DBP-DNA adducts were observed in both maternal and fetal tissues by ³³P postlabeling and HPLC analysis and were modulated by I3C and AHR genotype. I3C also modulated phase I and phase II enzyme protein expression in dams and gene expression in newborn thymus. I3C chemoprotection may involve modification of the bioavailability of DBP to the fetus and/or modulation of gene expression in the fetus as well. This is the first demonstration that transplacental exposure to an environmental PAH can induce a highly aggressive lymphoma in mice. These results raise the possibility that PAH exposures to pregnant women could contribute to similar cancers in children and young adults and, that the addition of chemoprotective agents to the maternal diet may reduce cancer risk among offspring. / Graduation date: 2006