- Email: [email protected]
1E-2 Childhood outcomes of early preterm birth impact of intrauterine growth restriction
S34 not classically imprinted can be passed at least to F2 following a dietary challenge in F0 pregnancy, and further following endocrine disruptor exposure. Effects may be sex-specific. They may be passed via both male and female lines. Multiple questions therefore arise: How uniform are the processes involved? Do they involve effects on the germline or via maternal adaptations during pregnancy? What fitness advantages do they confer (i.e. why have they endured)? Do the heritable processes from F1 to F2 wane if the inducing stimulus is not present in F1 , and does the presence of a stimulus in F1 amplify the effect passed to F2 ? Will different processes operate, or operate under different circumstances, in humans to those in the commonly used experimental species, and if so what strategies can we devise for studying them in humans? Mark Hanson is supported by the British Heart Foundation.
Session 1D. Implantation, Placentation and Early Life 1D-2 Environmental influences during preimplantation embryo development: the role of oxygen K.L. Kind1 *, M. Lane2 , J.G. Thompson2 . Research Centre for Reproductive Health, 1 Discipline of Agricultural and Animal Science, 2 Discipline of Obstetrics and Gynaecology, University of Adelaide, Adelaide, 5005, Australia E-mail: [email protected] Alterations in the environmental conditions experienced by the preimplantation embryo can have longer-term consequences for fetal, placental and postnatal development. The embryo adapts to changes in its environment with alterations in outcomes, including embryonic metabolism, gene expression and cell number. Oxygen is an important component of the preimplantation environment and embryos are exposed to varying oxygen conditions in vivo, and in vitro, during assisted reproductive technologies. Our studies have investigated the effects of exposing preimplantation embryos to varying oxygen conditions on subsequent development. Exposure of mouse embryos to reduced oxygen (2% vs 7 or 20% oxygen) during post-compaction embryo culture induces expression of oxygen-regulated genes, including glucose transporters-1 and -3, alters blastocyst glucose uptake and reduces cell number. Embryos cultured under low oxygen have reduced postimplantation development rates and fetal, but not placental weight, is reduced following embryo culture under low oxygen. Morphometric analysis of the placentas indicated no differences in proportions of junctional or labyrinthine exchange regions, but surface density (surface area/gram labyrinth) was reduced in placentas developed from embryos cultured at 2% oxygen. Species differences exist, however, as culture of postcompaction bovine embryos under low oxygen improves embryo quality and has marginal effects on oxygen-regulated gene expression. These studies indicate that the preimplantation embryo can detect and respond to changes in oxygen levels within its environment, and these adaptive changes have consequences for fetal and placental development. Our continuing studies are investigating the signalling mechanisms underlying the adaptive response of the oocyte and embryo to such environmental changes. 1D-3 Maternal environment and the early embryo: the origin of developmental adaptations persisting into adult life T.P. Fleming *, A.J. Watkins, J.J. Eckert, E. Ursell, M.A. Hanson. School of Biological Sciences, University of Southampton, Bassett Crescent East, Southampton SO16 7PX, UK E-mail: [email protected] The preimplantation period in several species is now recognised as a critical developmental window during which environmental conditions can influence the phenotype and long-term potential of the early embryo. In vitro culture, as practised in assisted
Invited Lectures conception treatment, as well as maternal dietary status in vivo, have the capacity to alter embryo homeostasis and, as shown in animal models, ultimately lead to changes in postnatal growth, physiology and behaviour that become associated with adult chronic disease. Recently, using a mouse maternal low protein diet (LPD) model, we have investigated the origin and propagation of embryo-derived programming. Our data indicate that the embryo is able to sense and respond to the levels of nutrients available to it especially by altering the properties of the extraembryonic lineages responsible for maternal-fetal nutrient delivery in later pregnancy. This compensatory process is activated by the blastocyst stage, involves both trophoblast and visceral endoderm derivatives, and appears critical in protecting fetal growth during conditions of adverse nutrient availability. For example, maternal LPD stimulates visceral yolk sac endocytosis of maternal proteins for histiotrophic fetal nutrition, apparently mediated through enhanced expression of the multi-ligand megalin receptor. However, if nutrient availability changes, the positive influence of the embryo response to secure the perinatal growth trajectory and presumably reproductive fitness becomes disadvantageous in later life with cardiovascular and metabolic consequences.
Session 1E. Preterm Birth and Its Consequences 1E-2 Childhood outcomes of early preterm birth intrauterine growth restriction
impact of
N. French *. Perth, Australia The double jeopardy of both preterm birth and intrauterine growth restriction (IUGR) has been associated with increased risks compared with either feature alone. Reports of outcomes, particularly of IUGR have varied widely in preterm birth in populations defined by either birthweight or gestation, but rarely both. In Western Australia (WA), extreme centralisation of high risk perinatal services to a single tertiary neonatal service, coupled with very high rates of tertiary inborn delivery (>90% of <32 w births), and a centralised follow up program have allowed us to examine preterm outcomes on a regional basis in both <32 w and <1500 g populations. This presentation examines two aspects of preterm outcome, (a) cerebral palsy (CP) and (b) cognitive outcomes in relation to growth status at birth. Whereas cerebral palsy overall is associated with poor intrauterine growth, this is not seen in preterm infants <32 weeks; rates of CP are as high or even higher in <31 w infants who are above 1500 g than in all those <1500 g. This paradoxical feature is consistent in three regional WA very preterm cohorts spanning 16 years and including nearly 1500 children, >100 with CP. At these gestations CP is related to underlying pregnancy problem more than to growth per se. Cognitive deficits in preterm infants have been associated with IUGR in multiple observational studies, but it is not clear whether these findings are related to the intrauterine environment per se or to confounding factors which influence both growth and later cognition. In an effort to control for genetic/environmental influences we examined later IQ scores in relation to the degree of growth discordance between same sex twin pairs in both term and very preterm populations, finding no IQ disadvantage in the smaller twin. This suggests that factors other than IUGR per se may be confounding previous studies.
Session 1D. Implantation, Placentation and Early Life 1D-2 Environmental influences during preimplantation embryo development: the role of oxygen K.L. Kind1 *, M. Lane2 , J.G. Thompson2 . Research Centre for Reproductive Health, 1 Discipline of Agricultural and Animal Science, 2 Discipline of Obstetrics and Gynaecology, University of Adelaide, Adelaide, 5005, Australia E-mail: [email protected] Alterations in the environmental conditions experienced by the preimplantation embryo can have longer-term consequences for fetal, placental and postnatal development. The embryo adapts to changes in its environment with alterations in outcomes, including embryonic metabolism, gene expression and cell number. Oxygen is an important component of the preimplantation environment and embryos are exposed to varying oxygen conditions in vivo, and in vitro, during assisted reproductive technologies. Our studies have investigated the effects of exposing preimplantation embryos to varying oxygen conditions on subsequent development. Exposure of mouse embryos to reduced oxygen (2% vs 7 or 20% oxygen) during post-compaction embryo culture induces expression of oxygen-regulated genes, including glucose transporters-1 and -3, alters blastocyst glucose uptake and reduces cell number. Embryos cultured under low oxygen have reduced postimplantation development rates and fetal, but not placental weight, is reduced following embryo culture under low oxygen. Morphometric analysis of the placentas indicated no differences in proportions of junctional or labyrinthine exchange regions, but surface density (surface area/gram labyrinth) was reduced in placentas developed from embryos cultured at 2% oxygen. Species differences exist, however, as culture of postcompaction bovine embryos under low oxygen improves embryo quality and has marginal effects on oxygen-regulated gene expression. These studies indicate that the preimplantation embryo can detect and respond to changes in oxygen levels within its environment, and these adaptive changes have consequences for fetal and placental development. Our continuing studies are investigating the signalling mechanisms underlying the adaptive response of the oocyte and embryo to such environmental changes. 1D-3 Maternal environment and the early embryo: the origin of developmental adaptations persisting into adult life T.P. Fleming *, A.J. Watkins, J.J. Eckert, E. Ursell, M.A. Hanson. School of Biological Sciences, University of Southampton, Bassett Crescent East, Southampton SO16 7PX, UK E-mail: [email protected] The preimplantation period in several species is now recognised as a critical developmental window during which environmental conditions can influence the phenotype and long-term potential of the early embryo. In vitro culture, as practised in assisted
Invited Lectures conception treatment, as well as maternal dietary status in vivo, have the capacity to alter embryo homeostasis and, as shown in animal models, ultimately lead to changes in postnatal growth, physiology and behaviour that become associated with adult chronic disease. Recently, using a mouse maternal low protein diet (LPD) model, we have investigated the origin and propagation of embryo-derived programming. Our data indicate that the embryo is able to sense and respond to the levels of nutrients available to it especially by altering the properties of the extraembryonic lineages responsible for maternal-fetal nutrient delivery in later pregnancy. This compensatory process is activated by the blastocyst stage, involves both trophoblast and visceral endoderm derivatives, and appears critical in protecting fetal growth during conditions of adverse nutrient availability. For example, maternal LPD stimulates visceral yolk sac endocytosis of maternal proteins for histiotrophic fetal nutrition, apparently mediated through enhanced expression of the multi-ligand megalin receptor. However, if nutrient availability changes, the positive influence of the embryo response to secure the perinatal growth trajectory and presumably reproductive fitness becomes disadvantageous in later life with cardiovascular and metabolic consequences.
Session 1E. Preterm Birth and Its Consequences 1E-2 Childhood outcomes of early preterm birth intrauterine growth restriction
impact of
N. French *. Perth, Australia The double jeopardy of both preterm birth and intrauterine growth restriction (IUGR) has been associated with increased risks compared with either feature alone. Reports of outcomes, particularly of IUGR have varied widely in preterm birth in populations defined by either birthweight or gestation, but rarely both. In Western Australia (WA), extreme centralisation of high risk perinatal services to a single tertiary neonatal service, coupled with very high rates of tertiary inborn delivery (>90% of <32 w births), and a centralised follow up program have allowed us to examine preterm outcomes on a regional basis in both <32 w and <1500 g populations. This presentation examines two aspects of preterm outcome, (a) cerebral palsy (CP) and (b) cognitive outcomes in relation to growth status at birth. Whereas cerebral palsy overall is associated with poor intrauterine growth, this is not seen in preterm infants <32 weeks; rates of CP are as high or even higher in <31 w infants who are above 1500 g than in all those <1500 g. This paradoxical feature is consistent in three regional WA very preterm cohorts spanning 16 years and including nearly 1500 children, >100 with CP. At these gestations CP is related to underlying pregnancy problem more than to growth per se. Cognitive deficits in preterm infants have been associated with IUGR in multiple observational studies, but it is not clear whether these findings are related to the intrauterine environment per se or to confounding factors which influence both growth and later cognition. In an effort to control for genetic/environmental influences we examined later IQ scores in relation to the degree of growth discordance between same sex twin pairs in both term and very preterm populations, finding no IQ disadvantage in the smaller twin. This suggests that factors other than IUGR per se may be confounding previous studies.