Kent Thornburg

Oregon Health and Science University | OHSU · Division of Cardiovascular Medicine

The concept of the early life developmental origins of health and disease (DOHaD) in adults has stimulated a new approach to understanding disease trajectories, with major public health implications. Indeed, the principle of the 'lifecourse of disease' now influences health policies internationally. Environmental influences during pregnancy and ear...

The endocrine and neuroendocrine system in pregnancy involves highly complex maternal, fetal and placental mechanisms, which are critical for the maintenance of pregnancy, the timing of parturition, for fetal growth and protection from adverse fetal programming. This timely book summarizes the different endocrine aspects related to pregnant women,...

Understanding, predicting, and preventing pregnancy disorders have been a major research target. Nonetheless, the lack of progress is illustrated by research results related to preeclampsia and other hypertensive pregnancy disorders. These remain a major cause of maternal and infant mortality worldwide. There is a general consensus that the rate of...

The majority of women in the United States do not meet recommendations for healthful nutrition and weight before and during pregnancy. Women and providers often ask what a healthy diet for a pregnant woman should look like. The message should be “eat better, not more.” This can be achieved by basing diet on a variety of nutrient dense, whole foods,...

Key points: The fetal heart relies on carbohydrates in utero and must be prepared to metabolize fatty acids after birth but the effects of compromised fetal growth on the maturation of this metabolic system are unknown. Plasma fatty-acylcarnitines are elevated in intrauterine growth restricted (IUGR) fetuses over control fetuses, indicative of imp...

Objective Increased infant birth weight and adiposity are associated with an altered risk of adult chronic diseases. The objective was to investigate the association between maternal dietary fat intake during pregnancy and newborn adiposity. Study design The study included 79 singleton pregnancies. Associations between maternal dietary fat intake...

The degree that maternal glycemia affects placental metabolism of trophoblast cell types [cytotrophoblast (CTB) and syncytiotrophoblast (SCT)] in pregnant persons with gestational diabetes mellitus (GDM) is unknown. We tested the hypotheses that (a) hyperglycemia suppresses the metabolic rates of CTB and SCT; and (b) low placental metabolic activit...

Cardiac pumping depends on the morphological structure of the heart, but also on its subcellular (ultrastructural) architecture, which enables cardiac contraction. In cases of congenital heart defects, localized ultrastructural disruptions that increase the risk of heart failure are only starting to be discovered. This is in part due to a lack of t...

Cardiac pumping depends on the morphological structure of the heart, but also on its subcellular (ultrastructural) architecture, which enables cardiac contraction. In cases of congenital heart defects, localized ultrastructural disruptions that increase the risk of heart failure are only starting to be discovered. This is in part due to a lack of t...

Cardiac pumping depends on the morphological structure of the heart, but also on its subcellular (ultrastructural) architecture, which enables cardiac contraction. In cases of congenital heart defects, localized ultrastructural disruptions that increase the risk of heart failure are only starting to be discovered. This is in part due to a lack of t...

Objectives Women with obesity are at increased risk to have large for gestational age neonates. Our study aimed to understand the association between maternal adiposity and neonatal adiposity and metabolic markers. Methods This was a prospective cohort study of healthy women with singleton pregnancies enrolled at 12–16 or 37–38 weeks gestation. Ma...

Objective: Women with overweight/obesity have significantly lower rates of exclusive breastfeeding (EBF) at 6 weeks postpartum compared with women of normal weight. We sought to determine whether differences in Baby-Friendly Hospital Initiative (BFHI) adherence, obstetric practices, or social support explain these weight-related EBF disparities. M...

Efficient cardiac pumping depends on the morphological structure of the heart, but also on its sub-cellular (ultrastructural) architecture, which enables cardiac contraction. In cases of congenital heart defects, localized sub-cellular disruptions in architecture that increase the risk of heart failure are only starting to be discovered. This is in...

Birthweight is a well-known predictor of adult-onset chronic disease. The placenta plays a necessary role in regulating fetal growth and determining birth size. Maternal stressors that affect placental function and prenatal growth include maternal overnutrition and undernutrition, toxic social stress, and exposure to toxic chemicals. These stressor...

Low weight in early infancy is a known risk factor for cardio-metabolic syndrome in adult life. However, little is known either about developmental programming in subjects of normal birthweight, or about events between the ages which separate early programming and the occurrence of disease at late adulthood. We tested the hypothesis that circulatin...

Professor David James Purslove Barker was a physician and one of the most influential medical scientists of our time. His fetal programming hypothesis (known as the Barker Hypothesis) transformed thinking about what causes chronic diseases that are the scourge of modern society: cancer, cardiovascular disease and diabetes. The Barker Hypothesis pro...

Multiscale Cardiac Imaging: From Whole Heart Images to Cardiac Ultrastructure - Volume 25 Supplement - Graham Rykiel, Claudia S. López, Jessica L. Riesterer, Melissa Williams, Katherine Courchaine, Alina Maloyan, Kent Thornburg, Sandra Rugonyi

This special issue for the Journal of Endocrinology celebrates the 30th anniversary of David Barker’s seminal findings that led to the scientific field of the Developmental Origins of Health and Disease (DOHaD). In 1989, Barker and colleagues reported that low birth weight and weight at one year, proxies for fetal growth restriction, were related t...

Fetal cardiomyocytes shift from glycolysis to oxidative phosphorylation around the time of birth. Myeloid ecotropic viral integration site 1 (MEIS1) is a transcription factor that promotes glycolysis in hematopoietic stem cells. We reasoned that MEIS1 could have a similar role in the developing heart. We hypothesized that suppression of MEIS1 expre...

Lipoapoptosis of cardiomyocytes may underlie diabetic cardiomyopathy. Numerous forms of cardiomyopathies share a common end-pathway in which apoptotic loss of cardiomyocytes is mediated by p38α mitogen activated protein kinase (MAPK). Although we have previously shown that palmitic acid (PA), a saturated fatty acid (SFA) elevated in plasma of type...

Cardiogenesis is interdependent with blood flow within the embryonic system. Recently, a number of studies have begun to elucidate the effects of hemodynamic forces acting upon and within cells as the cardiovascular system begins to develop. Changes in flow are picked up by mechanosensors in endocardial cells exposed to wall shear stress (the tange...

The fetal myocardium is known to be sensitive to hemodynamic load, responding to systolic overload with cellular hypertrophy, proliferation and accelerated maturation. However, the fetal cardiac growth response to primary volume overload is unknown. We hypothesized that increased venous return would stimulate fetal cardiomyocyte proliferation and t...

Key points: Plasma thyroid hormone (tri-iodo-l-thyronine; T3 ) concentrations rise near the end of gestation and is known to inhibit proliferation and stimulate maturation of cardiomyocytes before birth. Thyroid hormone receptors are required for the action of thyroid hormone in fetal cardiomyocytes. Loss of thyroid hormone receptor (TR)α1 abolish...

Exclusive breastfeeding (EBF) has numerous maternal health benefits. However, EBF rates are lower in mothers with obesity. We sought to better understand whether maternal body composition measurements in early pregnancy are also predictive of lower rates of EBF. Healthy pregnant women with pre‐pregnancy body mass index (BMI) of 17.5‐51 kg/m² underw...

Objective: Prenatal hypertension leads to mitral annular dilation and is linked to changes in valvular extracellular matrix (ECM) and cell cycle genes including TGFβ-1, BMPs and FGF. We hypothesized that these changes are exacerbated by additional mechanical stress. Methods: Fetal sheep received 8 days of plasma infusion to induce hypertension (HTN...

Pre-pregnancy (pregravid) obesity has been linked to several adverse health outcomes for both mother and offspring. Complications during pregnancy include increased risk for gestational diabetes, hypertension, preeclampsia, placental abruption, and difficulties during delivery. Several studies suggest that these negative outcomes are mediated by he...

Introduction: The placenta employs an efficient and selective fatty acid transport system to supply lipids for fetal development. Disruptions in placental fatty acid transport lead to restricted fetal growth along with cardiovascular and neurologic deficits. Nevertheless, little is known about the molecular mechanisms involved in human placental f...

Use of oral agents to treat gestational diabetes mellitus (GDM) remains controversial. Recent recommendations from the Society for Maternal Fetal Medicine (SMFM) assert that metformin may be a safe first line alternative to insulin for GDM treatment and preferable to glyburide. However, several issues should give pause to the widespread adoption of...

Objective: Higher body-mass index (BMI) and lower birth weight (BW) are associated with elevated risk of diabetes in adulthood, but the extent to which they compose two distinct pathways is unclear. Methods: We used data from the National Longitudinal Study of Adolescent to Adult Health, a cohort of adolescents (1994-1995) followed for 14 years...

Congenital heart defects (CHDs) represent the most common form of human birth defects; approximately one-third of heart defects involve malformations of the outflow tract (OFT). Maternal diabetes increases the risk of CHD by 3–5 fold. During heart organogenesis, little is known about the effects of hyperglycemia on hemodynamics, which are critical...

Epidemiologic studies identified the linkage between exposures to stresses, including the type and plane of nutrition in utero with development of disease in later life. Given the critical roles of the placenta in mediating transport of nutrients between the mother and fetus and regulation of maternal metabolism, recent attention has focused on the...

Blood flow is critical for normal cardiac development. Hemodynamic stimuli outside of normal ranges can lead to overt cardiac defects, but how early heart tissue remodels in response to altered hemodynamics is poorly understood. This study investigated changes in tissue collagen in response to hemodynamic overload in the chicken embryonic heart out...

There is limited knowledge about the metabolic reprogramming induced by cancer therapies and how this contributes to therapeutic resistance. Here we show that although inhibition of PI3K-AKT-mTOR signaling markedly decreased glycolysis and restrained tumor growth, these signaling and metabolic restrictions triggered autophagy, which supplied the me...

Prepregnancy maternal obesity is associated with adverse outcomes for the offspring, including increased incidence of neonatal bacterial sepsis and necrotizing enterocolitis. We recently reported that umbilical cord blood (UCB) monocytes from babies born to obese mothers generate a reduced IL-6/TNF-α response to TLR 1/2 and 4 ligands compared to th...

An international summit focusing on the difficult challenge of providing adequate nutrition for adolescent girls and young women in low- and middle-income countries was held in Portland, Oregon in 2015. Sixty-seven delegates from 17 countries agreed on a series of recommendations that would make progress toward improving the nutritional status of g...

Thromboembolic complications are a significant cause of mortality and re-hospitalization in heart failure (HF) patients. One source of thrombi is the ventricular endocardial surface that becomes increasingly pro-thrombotic as HF progresses. Anticoagulation comes with bleeding risks so identifying therapeutic agents for improving cardiac endothelial...

Objective: Maternal diet and gestational weight gain (GWG) influence birth weight and infant adiposity, which are important predictors of lifetime health. To better understand these relationships, we studied associations between maternal diet and GWG, adiposity, and birth weight in a well characterized cohort of pregnant women. Study design: Dat...

Adolescence is the period of development that begins at puberty and ends in early adulthood. Most commonly, adolescence is divided into three developmental periods: early adolescence (10–14 years of age), late adolescence (15–19 years of age), and young adulthood (20–24 years of age). Adolescence is marked by physical and sexual maturation, social...

Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialised topics. At IFPA meeting 2016 there were twelve themed workshops, four of which are summarized in this report. These workshops related to various aspects of placental biology but collectively covered areas of decidual-trophoblast interaction, regul...

Rapid weight gain in infancy and low levels of n-3 long chain polyunsaturated fatty acids (LCPUFA) at birth are associated with increased adiposity later in life. The association between placental LCPUFA delivery and weight gain in infancy is poorly understood. We sought to determine the relationships between maternal phenotype, placental fatty aci...

Background: Adverse prenatal development, often indicated by low birthweight, is associated with elevated risk of cardiometabolic disease, but the mediating role of obesity is not well understood. Methods: We used data from the National Longitudinal Study of Adolescent to Adult Health, a nationally representative sample of adolescents followed 14 y...

There is, perhaps, no parallel in history where massive numbers of people have rapidly become ill without an infectious agent as perpetrator. This article is protected by copyright. All rights reserved

The syncytiotrophoblast (SCT) at the maternal-fetal interface has been presumed to be the primary driver of placental metabolism, and the underlying progenitor cytotrophoblast cells (CTB) an insignificant contributor to placental metabolic activity. However, we now show that the metabolic rate of CTB is much greater than the SCT. The oxygen consump...

Although cardiac malformations at birth are typically associated with genetic anomalies, blood flow dynamics also play a crucial role in heart formation. However, the relationship between blood flow patterns in the early embryo and later cardiovascular malformation has not been determined. We used the chicken embryo model to quantify the extent to...

Abnormal blood flow during early cardiovascular development has been identified as a key factor in the pathogenesis of congenital heart disease; however, the mechanisms by which altered hemodynamics induce cardiac malformations are poorly understood. This study used outflow tract (OFT) banding to model increased afterload, pressure, and blood flow...

Epidemiological evidence links an individual’s susceptibility to chronic disease in adult life to events during their intrauterine phase of development. Biologically this should not be unexpected, for organ systems are at their most plastic when progenitor cells are proliferating and differentiating. Influences operating at this time can permanentl...

Epidemiology formed the basis of 'the Barker hypothesis', the concept of 'developmental programming' and today's discipline of the Developmental Origins of Health and Disease (DOHaD). Animal experimentation provided proof of the underlying concepts, and continues to generate knowledge of underlying mechanisms. Interventions in humans, based on DOHa...

The placenta is a key organ in programming the fetus for later disease. This review outlines eight of many structural and physiological features of the placenta which are associated with adult onset chronic disease. 1) Placental efficiency relates the placental mass to the fetal mass. Ratios at the extremes are related to cardiovascular disease ris...

Epidemiological evidence links an individual's susceptibility to chronic disease in adult life to events during their intrauterine phase of development. Biologically this should not be unexpected, for organ systems are at their most plastic when progenitor cells are proliferating and differentiating. Influences operating at this time can permanentl...

Objective: To compare long-term cardiovascular outcomes in survivors of fetal anaemia and intrauterine transfusion with those of non-anaemic siblings. Design: Retrospective cohort study. Setting: Auckland, New Zealand. Participants: Adults who received intrauterine transfusion for anaemia due to rhesus disease (exposed) and their unexposed s...

Subdivision-based image registration has previously been applied to co-localize digital information extracted from rigid structures in biological specimens, such as the brain. Here, we describe and demonstrate the creation and application of a two-dimensional subdivision-based atlas representing a dynamic structure: the outflow tract of the develop...

The fetus largely depends on maternal supply and placental transport for its source of long-chain polyunsaturated fatty acids (LCPUFAs), which are essential for proper neurological and cardiovascular development. Pregnancy complications such as diabetes reduces neonatal LCPUFA supply, but little is known of how fatty acid delivery is affected by ma...

The Developmental Origins of Health and Disease and the related science of epigenetics redefines the meaning of what constitutes upstream approaches to significant social and public health problems. An increasingly frequent concept being expressed is "When it comes to your health, your zip code may be more important than your genetic code". Epigene...

While the human placenta must provide selected long-chain fatty acids to support the developing fetal brain, little is known about the mechanisms underlying the transport process. We tracked the movement of the fluorescently labeled long-chain fatty acid analogue, BODIPY-C12, across the cell layers of living explants of human term placenta. Althoug...

Syncytialized cytotrophoblast contain few detectable BODIPY-C12 LDs. Cytotrophoblast cells cultured for 72hr were incubated with 2uM BODIPY-C12 for 30 mins, fixed, and immunolabeled with desmoplakin (1:200, ab16434, Abcam) as described in the methods section. Nuclei are stained with Hoechst dye. Imaging was performed using a Zeiss 880 LSM Confocal...

Time lapse confocal movie of human term placental explant over 30 minutes. BODIPY-C12 (green) is incorporated into cytotrophoblast lipid droplets (LipidTOX Far Red, red), but very little in syncytiotrophoblast. Time (min:sec). Dashed line represents the syncytiotrophoblast-cytotrophoblast interface. Magnification: 600X, Scale Bar: 5μm. (AVI)

Time lapse confocal movie of human term placental explant over 30 minutes over a larger field of view. This video illustrates a larger field of view and scans through the villus depth (0.2μm min-1). Similar to Movie S1, (BODIPY-C12 (green) is incorporated into cytotrophoblast lipid droplets (LD, LipidTOX Far Red, red), but very little in syncytiotr...