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Full-Text Articles in Medicine and Health Sciences
The Long And Short Of It: The Role Of Telomeres In Fetal Origins Of Adult Disease., Stephanie E Hallows, Timothy Regnault, Dean H Betts
The Long And Short Of It: The Role Of Telomeres In Fetal Origins Of Adult Disease., Stephanie E Hallows, Timothy Regnault, Dean H Betts
Paediatrics Publications
Placental insufficiency, maternal malnutrition, and other causes of intrauterine growth restriction (IUGR) can significantly affect short-term growth and long-term health. Following IUGR, there is an increased risk for cardiovascular disease and Type 2 Diabetes. The etiology of these diseases is beginning to be elucidated, and premature aging or cellular senescence through increased oxidative stress and DNA damage to telomeric ends may be initiators of these disease processes. This paper will explore the areas where telomere and telomerase biology can have significant effects on various tissues in the body in IUGR outcomes.
The Effect Of Intermittent Umbilical Cord Occlusion On Elastin Composition In The Ovine Fetus., Jennifer A Thompson, Sarah A Gimbel, Bryan S Richardson, Robert Gagnon, Timothy Regnault
The Effect Of Intermittent Umbilical Cord Occlusion On Elastin Composition In The Ovine Fetus., Jennifer A Thompson, Sarah A Gimbel, Bryan S Richardson, Robert Gagnon, Timothy Regnault
Paediatrics Publications
This study aimed to determine the effect of varying degrees of intermittent umbilical cord occlusion (UCO) on arterial elastin composition. Over 4 days, chronically catheterized late gestation fetal sheep received 5 total UCO per day lasting 1 min/h (mild group: n = 6), 2 min/h (moderate group: n = 4), 3 min/h (severe group; n = 6); or no occlusion (control group: n = 7). Each group was evaluated for elastin content of the carotid and superior mesenteric artery (SMA), the arterial pressure response to UCO, and plasma cortisol concentration. Elastin content of the carotid artery was significantly increased by …
Intrauterine Growth Restriction Increases Fetal Hepatic Gluconeogenic Capacity And Reduces Messenger Ribonucleic Acid Translation Initiation And Nutrient Sensing In Fetal Liver And Skeletal Muscle., Stephanie R Thorn, Timothy Regnault, Laura D Brown, Paul J Rozance, Jane Keng, Michael Roper, Randall B Wilkening, William W Hay, Jacob E Friedman
Intrauterine Growth Restriction Increases Fetal Hepatic Gluconeogenic Capacity And Reduces Messenger Ribonucleic Acid Translation Initiation And Nutrient Sensing In Fetal Liver And Skeletal Muscle., Stephanie R Thorn, Timothy Regnault, Laura D Brown, Paul J Rozance, Jane Keng, Michael Roper, Randall B Wilkening, William W Hay, Jacob E Friedman
Paediatrics Publications
Expression of key metabolic genes and proteins involved in mRNA translation, energy sensing, and glucose metabolism in liver and skeletal muscle were investigated in a late-gestation fetal sheep model of placental insufficiency intrauterine growth restriction (PI-IUGR). PI-IUGR fetuses weighed 55% less; had reduced oxygen, glucose, isoleucine, insulin, and IGF-I levels; and had 40% reduction in net branched chain amino acid uptake. In PI-IUGR skeletal muscle, levels of insulin receptor were increased 80%, whereas phosphoinositide-3 kinase (p85) and protein kinase B (AKT2) were reduced by 40%. Expression of eukaryotic initiation factor-4e was reduced 45% in liver, suggesting a unique mechanism limiting …
Effects Of Early Gestation Gh Administration On Placental And Fetal Development In Sheep., Casey D Wright, Ryan J Orbus, Timothy Regnault, Russell V Anthony
Effects Of Early Gestation Gh Administration On Placental And Fetal Development In Sheep., Casey D Wright, Ryan J Orbus, Timothy Regnault, Russell V Anthony
Paediatrics Publications
Ovine GH (oGH) is synthesized in placental tissue during maximal placental growth and development. Our objectives were to localize oGH mRNA in the placenta, and study the impact of exogenous GH on twin pregnancies during the normal window (35-55 days of gestational age; dGA) of placental expression. In situ hybridization localized oGH mRNA in uterine luminal epithelium but not in tissues of fetal origin. While maternal GH and IGF-I concentrations were increased (P
Chronic Late-Gestation Hypoglycemia Upregulates Hepatic Pepck Associated With Increased Pgc1alpha Mrna And Phosphorylated Creb In Fetal Sheep., Paul J Rozance, Sean W Limesand, James S Barry, Laura D Brown, Stephanie R Thorn, Dan Loturco, Timothy Regnault, Jacob E Friedman, William W Hay
Chronic Late-Gestation Hypoglycemia Upregulates Hepatic Pepck Associated With Increased Pgc1alpha Mrna And Phosphorylated Creb In Fetal Sheep., Paul J Rozance, Sean W Limesand, James S Barry, Laura D Brown, Stephanie R Thorn, Dan Loturco, Timothy Regnault, Jacob E Friedman, William W Hay
Paediatrics Publications
Hepatic glucose production is normally activated at birth but has been observed in response to experimental hypoglycemia in fetal sheep. The cellular basis for this process remains unknown. We determined the impact of 2 wk of fetal hypoglycemia during late gestation on enzymes responsible for hepatic gluconeogenesis, focusing on the insulin-signaling pathway, transcription factors, and coactivators that regulate gluconeogenesis. Hepatic phosphoenolpyruvate carboxykinase and glucose-6-phosphatase mRNA increased 12-fold and 7-fold, respectively, following chronic hypoglycemia with no change in hepatic glycogen. Chronic hypoglycemia decreased fetal plasma insulin with no change in glucagon but increased plasma cortisol 3.5-fold. Peroxisome proliferator-activated receptor-gamma coactivator-1alpha mRNA …
The Expression Of Ovine Placental Lactogen, Star And Progesterone-Associated Steroidogenic Enzymes In Placentae Of Overnourished Growing Adolescent Ewes., Richard G Lea, Peter Wooding, Ian Stewart, Lisa T Hannah, Stephen Morton, Karen Wallace, Raymond P Aitken, John S Milne, Timothy Regnault, Russell V Anthony, Jacqueline M Wallace
The Expression Of Ovine Placental Lactogen, Star And Progesterone-Associated Steroidogenic Enzymes In Placentae Of Overnourished Growing Adolescent Ewes., Richard G Lea, Peter Wooding, Ian Stewart, Lisa T Hannah, Stephen Morton, Karen Wallace, Raymond P Aitken, John S Milne, Timothy Regnault, Russell V Anthony, Jacqueline M Wallace
Paediatrics Publications
Overnourishing pregnant adolescent sheep promotes maternal growth but reduces placental mass, lamb birth weight and circulating progesterone. This study aimed to determine whether altered progesterone reflected transcript abundance for StAR (cholesterol transporter) and the steroidogenic enzymes (Cyp11A1, Hsd3b and Cyp17). Circulating and placental expression of ovine placental lactogen (oPL) was also investigated. Adolescent ewes with singleton pregnancies were fed high (H) or moderate (M) nutrient intake diets to restrict or support placental growth. Experiment 1: peripheral progesterone and oPL concentrations were measured in H (n=7) and M (n=6) animals across gestation (days 7-140). Experiment 2: progesterone was measured to mid- …
Altered Placental And Fetal Expression Of Igfs And Igf-Binding Proteins Associated With Intrauterine Growth Restriction In Fetal Sheep During Early And Mid-Pregnancy., Barbra De Vrijer, Meredith L Davidsen, Randall B Wilkening, Russell V Anthony, Timothy Regnault
Altered Placental And Fetal Expression Of Igfs And Igf-Binding Proteins Associated With Intrauterine Growth Restriction In Fetal Sheep During Early And Mid-Pregnancy., Barbra De Vrijer, Meredith L Davidsen, Randall B Wilkening, Russell V Anthony, Timothy Regnault
Paediatrics Publications
The insulin-like growth factors (IGFs) are postulated to be altered in association with the development of intrauterine growth restriction (IUGR). The present studies examined placental and fetal hepatic mRNA concentration of components of the IGF system at two time points (55 and 90 d gestational age, dGA; Term 147 dGA) in a hyperthermia (HT)-induced sheep model of placental insufficiency-IUGR. Maternal plasma insulin and IGF-I were constant at 55 and 90 dGA and were unaffected by treatment. Umbilical vein insulin concentrations tended to be reduced at 90 dGA following HT exposure. Caruncle IGF-I mRNA was increased at 90 dGA in HT …
Placental Expression Of Angiopoietin-1, Angiopoietin-2 And Tie-2 During Placental Development In An Ovine Model Of Placental Insufficiency-Fetal Growth Restriction., Amy S Erickson Hagen, Ryan J Orbus, Randall B Wilkening, Timothy Regnault, Russell V Anthony
Placental Expression Of Angiopoietin-1, Angiopoietin-2 And Tie-2 During Placental Development In An Ovine Model Of Placental Insufficiency-Fetal Growth Restriction., Amy S Erickson Hagen, Ryan J Orbus, Randall B Wilkening, Timothy Regnault, Russell V Anthony
Paediatrics Publications
Fetal growth restriction (FGR) is associated with increased perinatal morbidity and mortality, and often results from functional placental insufficiency. Placentation requires extensive vasculogenesis and subsequent angiogenesis, in both maternal and fetal tissues. Angiopoietin-1 (Ang-1) and Angiopoietin-2 (Ang-2) are angiogenic growth factors expressed in the placenta, and compete for binding to a common receptor, Tunica interna endothelial cell kinase-2 (Tie-2). Our objective was to examine Ang-1, Ang-2 and Tie-2 expression in ovine placental tissue obtained from normal and FGR pregnancies throughout gestation. Fetal cotyledon and maternal caruncle tissue concentrations of Ang-1, Ang-2 and Tie-2 mRNA were assessed by real-time reverse transcriptase-polymerase …
Investigating The Causes Of Low Birth Weight In Contrasting Ovine Paradigms., J M Wallace, Timothy Regnault, S W Limesand, W W Hay, R V Anthony
Investigating The Causes Of Low Birth Weight In Contrasting Ovine Paradigms., J M Wallace, Timothy Regnault, S W Limesand, W W Hay, R V Anthony
Paediatrics Publications
Intrauterine growth restriction (IUGR) still accounts for a large incidence of infant mortality and morbidity worldwide. Many of the circulatory and transport properties of the sheep placenta are similar to those of the human placenta and as such, the pregnant sheep offers an excellent model in which to study the development of IUGR. Two natural models of ovine IUGR are those of hyperthermic exposure during pregnancy, and adolescent overfeeding, also during pregnancy. Both models yield significantly reduced placental weights and an asymmetrically growth-restricted fetus, and display altered maternal hormone concentrations, indicative of an impaired trophoblast capacity. Additionally, impaired placental angiogenesis …