An electrophoretic analysis of the coelomic and blood sera of the developing and metamorphosing bullfrog tadpole (Rana catesbeiana)

Albumin, as a percent of total proteins in both the coelomic serum and the blood serum, was determined for four groups of developing Rana catesbeiana tadpoles by cellulose acetate electrophoresis. Also, using Folin phenol reagent, the total protein of each the blood serum of metamorphosing tadpoles and the coelomic serum was determined, along with the coelomic fluid weights relative to the total body weights of these tadpoles. Coelomic fluid cells were identified and percentages for them calculated. Blood protein levels (1.68±SE 0.01 g/100 ml) are significantly higher than the coelomic fluid proteins (1.04±SE 0.01 g/100 ml) in metamorphosing animals. The percentage of albumin of total protein in the coelomic fluid (Group I, 18.3±2.3; II, 21.5±1.07; III, 22.7±0.68; IV, 31.3±1.25) is significantly higher than that in the blood (Group I, 18.3±2.30; II, 18.2±0.82; III, 20.1±0.82; IV, 27.7±1.16) for the last three Developmental Groups (Gosner stages 32-46). Percentages of albumin in the blood and in the coelomic fluid did not appear to increase at p<0.05, except in the last Group (IV). The coelomic fluid weight decreased during the last five metamorphic stages both absolutely, and also relative to tadpole weight. The majority of the coelomic cells identified were lymphocytes (51-85%). Monocytes accounted for 3-14%, and eosinophiles, erythrocytes, histiocytes, neutrophiles and thrombocytes combined, accounted for 4-23%

Placental Origins of Chronic Disease.

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 permanently affect their structure and functional capacity, and the activity of enzyme systems and endocrine axes. It is now appreciated that such effects lay the foundations for a diverse array of diseases that become manifest many years later, often in response to secondary environmental stressors. Fetal development is underpinned by the placenta, the organ that forms the interface between the fetus and its mother. All nutrients and oxygen reaching the fetus must pass through this organ. The placenta also has major endocrine functions, orchestrating maternal adaptations to pregnancy and mobilizing resources for fetal use. In addition, it acts as a selective barrier, creating a protective milieu by minimizing exposure of the fetus to maternal hormones, such as glucocorticoids, xenobiotics, pathogens, and parasites. The placenta shows a remarkable capacity to adapt to adverse environmental cues and lessen their impact on the fetus. However, if placental function is impaired, or its capacity to adapt is exceeded, then fetal development may be compromised. Here, we explore the complex relationships between the placental phenotype and developmental programming of chronic disease in the offspring. Ensuring optimal placentation offers a new approach to the prevention of disorders such as cardiovascular disease, diabetes, and obesity, which are reaching epidemic proportions.The authors thank the various funding agencies that have generously supported their research over the years; GJB, the Medical Research Council, the Wellcome Trust and Action Medical Research; ALF, the Biotechnology and Biological Sciences Council, the Medical Research Council and the Wellcome Trust; KLT, the National Institutes of Child Health and Human Development, the Nation Heart Lung and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Aging, the American Heart Association and the M. Lowell Edwards Endowment.This is the author accepted manuscript. The final version is available from the American Physiological Society via https://doi.org/10.1152/physrev.00029.201

4-D Computational Modeling of Cardiac Outflow Tract Hemodynamics over Looping Developmental Stages in Chicken Embryos

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 tangential force exerted by blood flow) and by myocardial and mesenchymal cells exposed to cyclic strain (deformation). Mechanosensors stimulate a variety of mechanotransduction pathways which elicit functional cellular responses in order to coordinate the structural development of the heart and cardiovascular system. The looping stages of heart development are critical to normal cardiac morphogenesis and have previously been shown to be extremely sensitive to experimental perturbations in flow, with transient exposure to altered flow dynamics causing severe late stage cardiac defects in animal models. This paper seeks to expand on past research and to begin establishing a detailed baseline for normal hemodynamic conditions in the chick outflow tract during these critical looping stages. Specifically, we will use 4-D (3-D over time) optical coherence tomography to create in vivo geometries for computational fluid dynamics simulations of the cardiac cycle, enabling us to study in great detail 4-D velocity patterns and heterogeneous wall shear stress distributions on the outflow tract endocardium. This information will be useful in determining the normal variation of hemodynamic patterns as well as in mapping hemodynamics to developmental processes such as morphological changes and signaling events during and after the looping stages examined here

From Fatalism to Mitigation: a Conceptual Framework for Mitigating Fetal Programming of Chronic Disease by Maternal Obesity

Prenatal development is recognized as a critical period in the etiology of obesity and cardiometabolic disease. Potential strategies to reduce maternal obesity-induced risk later in life have been largely overlooked. In this paper, we first propose a conceptual framework for the role of public health and preventive medicine in mitigating the effects of fetal programming. Second, we review a small but growing body of research (through August 2015) that examines interactive effects of maternal obesity and two public health foci – diet and physical activity – in the offspring. Results of the review support the hypothesis that diet and physical activity after early life can attenuate disease susceptibility induced by maternal obesity, but human evidence is scant. Based on the review, we identify major gaps relevant for prevention research, such as characterizing the type and dose response of dietary and physical activity exposures that modify the adverse effects of maternal obesity in the offspring. Third, we discuss potential implications of interactions between maternal obesity and postnatal dietary and physical activity exposures for interventions to mitigate maternal obesity-induced risk among children. Our conceptual framework, evidence review, and future research directions offer a platform to develop, test, and implement fetal programming mitigation strategies for the current and future generations of children

Long-Term Effects of Placental Growth on Overweight and Body Composition

Obesity is programmed in utero and small babies generally have small placentas. In some circumstances, an undernourished fetus can expand its placental surface to extract more nutrients. We hypothesize that this results in an imbalanced nutrient supply to the fetus leading to obesity. To determine whether placental size determines overweight and body composition, we studied 2003 subjects in adult life. Associations between placental surface area and indices of overweight were restricted to people who carried the Pro12Pro genotype of the PPARγ2 gene. For every 1 SD increase in placental surface area, the odds ratio for overweight was 1.37 (95% CI 1.10 to 1.71; P = 0.005). Expansion of the placental surface in compensation for fetal undernutrition increases the risk of overweight and a higher body fat percentage in people carrying the Pro12Pro genotype. We suggest that similar underlying multifactorial mechanisms affect the development of obesity in general

The Importance of Nutrition in Pregnancy and Lactation: Lifelong Consequences.

Most women in the United States do not meet the 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, including fruits, vegetables, legumes, whole grains, healthy fats with omega-3 fatty acids that include nuts and seeds, and fish, in place of poorer quality highly processed foods. Such a diet embodies nutritional density and is less likely to be accompanied by excessive energy intake than the standard American diet consisting of increased intakes of processed foods, fatty red meat, and sweetened foods and beverages. Women who report “prudent” or “health-conscious” eating patterns before and/or during pregnancy may have fewer pregnancy complications and adverse child health outcomes. Comprehensive nutritional supplementation (multiple micronutrients plus balanced protein energy) among women with inadequate nutrition has been associated with improved birth outcomes, including decreased rates of low birthweight. A diet that severely restricts any macronutrient class should be avoided, specifically the ketogenic diet that lacks carbohydrates, the Paleo diet because of dairy restriction, and any diet characterized by excess saturated fats. User-friendly tools to facilitate a quick evaluation of dietary patterns with clear guidance on how to address dietary inadequacies and embedded support from trained healthcare providers are urgently needed. Recent evidence has shown that although excessive gestational weight gain predicts adverse perinatal outcomes among women with normal weight, the degree of prepregnancy obesity predicts adverse perinatal outcomes to a greater degree than gestational weight gain among women with obesity. Furthermore, low body mass index and insufficient gestational weight gain are associated with poor perinatal outcomes. Observational data have shown that first-trimester gain is the strongest predictor of adverse outcomes. Interventions beginning in early pregnancy or preconception are needed to prevent downstream complications for mothers and their children. For neonates, human milk provides personalized nutrition and is associated with short- and long-term health benefits for infants and mothers. Eating a healthy diet is a way for lactating mothers to support optimal health for themselves and their infants

Maturation of the angiotensin II cardiovascular response in the embryonic White Leghorn chicken (Gallus gallus)

Angiotensin II (Ang II) is an important regulator of cardiovascular function in adult vertebrates. Although its role in regulating the adult system has been extensively investigated, the cardiovascular response to Ang II in embryonic vertebrates is relatively unknown. We investigated the potential of Ang II as a regulator of cardiovascular function in embryonic chickens, which lack central nervous system control of cardiovascular function throughout the majority of incubation. The cardiovascular response to Ang II in embryonic chickens was investigated over the final 50% of their development. Ang II produced a dose-dependent increase in arterial pressure on each day of development studied, and the response increased in intensity as development progressed. The Ang II type-1 receptor nonspecific competitive peptide antagonist [Sar1 ile8] Ang II blocked the cardiovascular response to subsequent injections of Ang II on day 21 only. The embryonic pressure response to Ang II (hypertension only) differed from that of adult chickens, in which initial hypotension is followed by hypertension. The constant level of gene expression for the Ang II receptor, in conjunction with an increasing pressure response to the peptide, suggests that two Ang II receptor subtypes are present during chicken development. Collectively, the data indicate that Ang II plays an important role in the cardiovascular development of chickens; however, its role in maintaining basal function requires further study