Talk:Abnormal Development - Developmental Origins of Health and Disease
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Cite this page: Hill, M.A. (2021, June 22) Embryology Abnormal Development - Developmental Origins of Health and Disease. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Talk:Abnormal_Development_-_Developmental_Origins_of_Health_and_Disease
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Developmental Origins of Metabolic Disease
Almost 2 billion adults in the world are overweight and more than half of them are classified as obese while nearly 1/3 of children globally experience poor growth and development. Given the vast amount of knowledge that has been gleaned from decades of research on growth and development, a number of questions remains as to why the world is now in the midst of a global epidemic of obesity accompanied by the "double burden of malnutrition" where overweight coexists with underweight and micronutrient deficiencies. This challenge to the human condition can be attributed to nutritional and environmental exposures during pregnancy that may program a fetus to have a higher risk of chronic diseases in adulthood. To explore this concept, frequently called the developmental origins of health and disease (DOHaD) or metabolic diseases (DOMD), this review considers a host of factors and physiological mechanisms that drive a fetus or child towards a higher risk of obesity, fatty liver disease, hypertension, and/or type 2 diabetes (T2D). To that end, this review explores the epidemiology of DOHaD with discussions focused on adaptations to human energetics, placental developmental, dysmetabolism, and key environmental exposures that act to promote chronic diseases in adulthood. These areas are complementary and additive in understanding how providing the best conditions for optimal growth can create the best possible conditions for lifelong health. Moreover, understanding both physiological as well as epigenetic and molecular mechanisms for DOMD is vital to most fully address the global issues of obesity and other chronic diseases.
Safi-Stibler S & Gabory A. (2019). Epigenetics and the Developmental Origins of Health and Disease: Parental environment signalling to the epigenome, critical time windows and sculpting the adult phenotype. Semin. Cell Dev. Biol. , , . PMID: 31587964 DOI.
Epigenetics and the Developmental Origins of Health and Disease: Parental environment signalling to the epigenome, critical time windows and sculpting the adult phenotype.
Abstract The literature about Developmental Origins of Health and Disease (DOHaD) studies is considerably growing. Maternal and paternal environment, during all the development of the individual from gametogenesis to weaning and beyond, as well as the psychosocial environment in childhood and teenage, can shape the adult and the elderly person's susceptibility to her/his own environment and diseases. This non-conventional, non-genetic, inheritance is underlain by several mechanisms among which epigenetics is obviously central, due to the notion of memory of early decisional events during development even when this stimulus is gone, that is implied in Waddington's developmental concept. This review first summarizes the different mechanisms by which the environment can model the epigenome: receptor signalling, energy metabolism and signal mechanotransduction from extracellular matrix to chromatin. Then an overview of the epigenetic changes in response to maternal environment during the vulnerability time windows, gametogenesis, early development, placentation and foetal growth, and postnatal period, is described, with the specific example of overnutrition and food deprivation. The implication of epigenetics in DOHaD is obvious, however the precise causal chain from early environment to the epigenome modifications to the phenotype still needs to be deciphered. Copyright © 2019 Elsevier Ltd. All rights reserved. KEYWORDS: Developmental origins of health and disease (DOHaD); Epigenetics; Non-communicable diseases; Nutrition PMID: 31587964 DOI: 10.1016/j.semcdb.2019.09.008
Acrylamide: A review about its toxic effects in the light of Developmental Origin of Health and Disease (DOHaD) concept
Food Chem. 2019 Jun 15;283:422-430. doi: 10.1016/j.foodchem.2019.01.054. Epub 2019 Jan 17.
Matoso V1, Bargi-Souza P2, Ivanski F1, Romano MA1, Romano RM3. Author information Abstract The endocrine system is highly sensitive to endocrine-disrupting chemicals (EDC) which interfere with metabolism, growth and reproduction throughout different periods of life, especially in the embryonic and pubertal stages, in which gene reprogramming may be associated with impaired development and control of tissues/organs even in adulthood. Acrylamide is considered a potential EDC and its main source comes from fried, baked and roasted foods that are widely consumed by children, teenagers and adults around the world. This review aimed to present some aspects regarding the acrylamide formation, its toxicokinetics, the occurrence of acrylamide in foods, the recent findings about its effects on different systems and the consequences for the human healthy. The challenges to characterize the molecular mechanisms triggered by acrylamide and to establish safe levels of consumption and/or exposure are also discussed in the present review.
Copyright © 2019 Elsevier Ltd. All rights reserved.
KEYWORDS: Acrylamide; Endocrine-disrupting chemical; Heated food; Nervous system; Reproductive toxicology; Thyroid hormone PMID: 30722893 DOI: 10.1016/j.foodchem.2019.01.054
Prof. Ralph Nanan is Chair and Professor of Paediatrics at the Sydney Medical School Nepean and Sub-dean of Research. He is also the Director of the Charles Perkins Centre Nepean and leads the Developmental Origins of Health and Disease project node. Professor Nanan started his scientific career in Paediatrics at the Children’s University Hospital in Wuerzburg, Germany, where he completed his PhD in 1991 in basic immunology. He then completed the Habilitation, which is the highest German academic degree, in 2002 in clinical immunology, before accepting the position of Director of Paediatrics at Nepean Hospital in 2003 and then his current position in 2005.Since beginning at Nepean, Professor Nanan has established a paediatric immunology laboratory and developed a comprehensive paediatric allergy service. He has also been heavily involved in policy development on a state level. Professor Nanan is a Chief Investigator on several clinical cohort studies. Apart from this, he has multiple teaching and supervisory responsibilities at the University of Sydney and regularly speaks at national and international conferences. Professor Nanan’s main areas of interest are the developmental origins of health and disease with a specific focus on paediatric clinical immunology, allergy and perinatology. Email: email@example.com
Growth hormone actions during development influence adult phenotype and longevity
Exp Gerontol. 2016 Jan 2. pii: S0531-5565(15)30109-1. doi: 10.1016/j.exger.2015.12.011. [Epub ahead of print]
Bartke A1, Sun L2, Fang Y2, Hill C2.
There is considerable evidence that exposure to undernutrition, overnutrition, stress or endocrine disruptors during fetal development can increase the probability of obesity, hypertension, cardiovascular disease and other problems in adult life. In contrast to these findings, reducing early postnatal growth by altering maternal diet or number of pups in a litter can increase longevity. In hypopituitary Ames dwarf mice, which are remarkably long lived, a brief period of growth hormone therapy starting at 1 or 2weeks of age reduces longevity and normalizes ("rescues") multiple aging-related traits. Collectively, these findings indicate that nutritional and hormonal signals during development can have profound impact on the trajectory of aging. We suspect that altered "programming" of aging during development may represent one of the mechanisms of the Developmental Origins of Health and Disease (DOHaD) and the detrimental effects of "catch-up" growth. Copyright © 2015. Published by Elsevier Inc. KEYWORDS: Aging; Ames dwarf mice; Developmental origin of disease; Developmental programming; Growth hormone; Litter crowding; Nutrition
Early origins of adult disease: Low birth weight and vascular remodeling
Atherosclerosis. 2014 Sep 30;237(2):391-399. doi: 10.1016/j.atherosclerosis.2014.09.027. [Epub ahead of print]
Visentin S1, Grumolato F1, Nardelli GB1, Di Camillo B2, Grisan E2, Cosmi E3.
Cardiovascular diseases (CVD) and diabetes still represent the main cause of mortality and morbidity in the industrialized world. Low birth weight (LBW), caused by intrauterine growth restriction (IUGR), was recently known to be associated with increased rates of CVD and non-insulin dependent diabetes in adult life (Barker's hypothesis). Well-established animal models have shown that environmentally induced IUGR (diet, diabetes, hormone exposure, hypoxia) increases the risk of a variety of diseases later in life with similar phenotypic outcomes in target organs. This suggests that a range of disruptions in fetal and postnatal growth may act through common pathways to regulate the developmental programming and produce a similar adult phenotype. The identification of all involved signaling cascades, underlying the physiopathology of these damages in IUGR fetuses, with their influence on adult health, is still far from satisfactory. The endothelium may be important for long-term remodeling and in the control of elastic properties of the arterial wall. Several clinical and experimental studies showed that IUGR fetuses, neonates, children and adolescents present signs of endothelial dysfunction, valuated by aorta intima media thickness, carotid intima media thickness and stiffness, central pulse wave velocity, brachial artery flow-mediated dilation, laser Doppler skin perfusion and by the measure of arterial blood pressure. In utero identification of high risk fetuses and long-term follow-up are necessary to assess the effects of interventions aimed at preventing pregnancy-induced hypertension, reducing maternal obesity, encouraging a healthy life style and preventing childhood obesity on adult blood pressure and cardiovascular disease in later life. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved. KEYWORDS: Cardiovascular disease; Fetal programming; Intrauterine growth restriction; Long-term consequences
Use Of A Mouse In Vitro Fertilization Model To Understand The Developmental Origins Of Health And Disease Hypothesis
Endocrinology. 2014 Mar 31:en20132081. [Epub ahead of print]
Feuer SK1, Liu X, Donjacour A, Lin W, Simbulan RK, Giritharan G, Piane LD, Kolahi K, Ameri K, Maltepe E, Rinaudo PF. Author information
Abstract The Developmental Origins of Health and Disease hypothesis holds that alterations to homeostasis during critical periods of development can predispose individuals to adult-onset chronic diseases like diabetes and metabolic syndrome. It remains controversial whether preimplantation embryo manipulation, clinically used to treat patients with infertility, disturbs homeostasis and affects long-term growth and metabolism. To address this controversy, we have assessed the effects of in vitro fertilization (IVF) on postnatal physiology in mice. We demonstrate that IVF and embryo culture, even under conditions considered optimal for mouse embryo culture, alter postnatal growth trajectory, fat accumulation and glucose metabolism in adult mice. Unbiased metabolic profiling in serum and microarray analysis of pancreatic islets and insulin sensitive tissues (liver, skeletal muscle and adipose tissue) revealed broad changes in metabolic homeostasis, characterized by systemic oxidative stress and mitochondrial dysfunction. Adopting a candidate approach, we identify thioredoxin-interacting protein (TXNIP)-a key molecule involved in integrating cellular nutritional and oxidative states with metabolic response-as a marker for preimplantation stress and demonstrate tissue-specific epigenetic and transcriptional TXNIP misregulation in selected adult tissues. Importantly, dysregulation of TXNIP expression was associated with enrichment for H4 acetylation at the Txnip promoter that persisted from the blastocyst stage through adulthood in adipose tissue. Our data supports the vulnerability of preimplantation embryos to environmental disturbance, and demonstrates that conception by IVF can reprogram metabolic homeostasis through metabolic, transcriptional, and epigenetic mechanisms with lasting effects for adult growth and fitness. This study has wide clinical relevance and underscores the importance of continued follow-up of IVF-conceived offspring.
Professor David Barker FRS, born 29 June 1938; died 27 August 2013.
Patterns of placental pathology in preterm premature rupture of membranes
J Dev Orig Health Dis. 2013 Jun;4(3):249-255.
Armstrong-Wells J1, Post MD, Donnelly M, Manco-Johnson MJ, Fisher BM, Winn VD. Author information
Inflammation is associated with preterm premature rupture of membranes (PPROM) and adverse neonatal outcomes. Subchorionic thrombi, with or without inflammation, may also be a significant pathological finding in PPROM. Patterns of inflammation and thrombosis may give insight into mechanisms of adverse neonatal outcomes associated with PPROM. To characterize histologic findings of placentas from pregnancies complicated by PPROM at altitude, 44 placentas were evaluated for gross and histological indicators of inflammation and thrombosis. Student's t-test (or Mann-Whitney U-test), χ2 analysis (or Fisher's exact test), mean square contingency and logistic regression were used when appropriate. The prevalence of histologic acute chorioamnionitis (HCA) was 59%. Fetal-derived inflammation (funisitis and chorionic plate vasculitis) was seen at lower frequency (30% and 45%, respectively) and not always in association with HCA. There was a trend for Hispanic women to have higher odds of funisitis (OR = 5.9; P = 0.05). Subchorionic thrombi were seen in 34% of all placentas. The odds of subchorionic thrombi without HCA was 6.3 times greater that the odds of subchorionic thrombi with HCA (P = 0.02). There was no difference in gestational age or rupture-to-delivery interval, with the presence or absence of inflammatory or thrombotic lesions. These findings suggest that PPROM is caused by or can result in fetal inflammation, placental malperfusion, or both, independent of gestational age or rupture-to-delivery interval; maternal ethnicity and altitude may contribute to these findings. Future studies focused on this constellation of PPROM placental findings, genetic polymorphisms and neonatal outcomes are needed. KEYWORDS: altitude, chorioamnionitis, fetal inflammatory response, funisitis, subchorionic thrombi
Delivery of a small for gestational age infant and greater maternal risk of ischemic heart disease
PLoS One. 2012;7(3):e33047. Epub 2012 Mar 14.
Bukowski R, Davis KE, Wilson PW. Source Medical Branch, Department of Obstetrics and Gynecology, University of Texas, Galveston, Texas, United States of America.
BACKGROUND: Delivery of a small for gestational age (SGA) infant has been associated with increased maternal risk of ischemic heart disease (IHD). It is uncertain whether giving birth to SGA infant is a specific determinant of later IHD, independent of other risk factors, or a marker of general poor health. The purpose of this study was to investigate the association between delivery of a SGA infant and maternal risk for IHD in relation to traditional IHD risk factors. METHODS AND FINDINGS: Risk of maternal IHD was evaluated in a population based cross-sectional study of 6,608 women with a prior live term birth who participated in the National Health and Nutrition Examination Survey (1999-2006), a probability sample of the U.S. population. Sequence of events was determined from age at last live birth and at diagnosis of IHD. Delivery of a SGA infant is strongly associated with greater maternal risk for IHD (age adjusted OR; 95% CI: 1.8; 1.2, 2.9; p = 0.012). The association was independent of the family history of IHD, stroke, hypertension and diabetes (family history-adjusted OR; 95% CI: 1.9; 1.2, 3.0; p = 0.011) as well as other risk factors for IHD (risk factor-adjusted OR; 95% CI: 1.7; 1.1, 2.7; p = 0.025). Delivery of a SGA infant was associated with earlier onset of IHD and preceded it by a median of 30 (interquartile range: 20, 36) years. CONCLUSIONS: Giving birth to a SGA infant is strongly and independently associated with IHD and a potential risk factor that precedes IHD by decades. A pregnancy that produces a SGA infant may induce long-term cardiovascular changes that increase risk for IHD.
Prenatal exposure to PCDDs/PCDFs and dioxin-like PCBs in relation to birth weight
Konishi K, Sasaki S, Kato S, Ban S, Washino N, Kajiwara J, Todaka T, Hirakawa H, Hori T, Yasutake D, Kishi R. Environ Res. 2009 Oct;109(7):906-13. Epub 2009 Aug 14.
Several human studies have shown that low-level exposure to environmental contaminants, such as polychlorinated biphenyls (PCBs) and organochlorine pesticides, negatively influences birth outcomes. However, the effects of low-level exposure to polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and dioxin-like PCBs (DL-PCBs) on birth outcomes have not been clarified in human studies. A prospective cohort study was established to investigate the possible adverse effects of PCDDs/PCDFs and DL-PCBs on fetal growth and neurodevelopment. We recruited 514 pregnant women between July 2002 and October 2005 in Sapporo, Japan. We measured 29 congener levels of PCDDs/PCDFs and DL-PCBs in maternal blood. Using multiple liner regression analysis of the association between birth weight and the levels of PCDDs/PCDFs and DL-PCBs with full adjustments for potential confounders, a significant adverse effect was observed regarding total PCDDs toxic equivalents (TEQ) levels (adjusted beta=-231.5g, 95% CI: -417.4 to -45.6) and total PCDFs TEQ levels (adjusted beta=-258.8g, 95% CI: -445.7 to -71.8). Among male infants, significant adverse associations with birth weight were found for total PCDDs TEQ level, total PCDDs/PCDFs TEQ level, and total TEQ level. However, among female infants, these significant adverse associations were not found. With regard to individual congeners of PCDDs/PCDFs and DL-PCBs, we found significantly negative association with the levels of 2,3,4,7,8-PeCDF (adjusted beta=-24.5g, 95% CI: -387.4 to -61.5). Our findings suggest that prenatal low-level exposure to PCDDs and PCDFs, especially 2,3,4,7,8-PeCDF, may accumulate in the placenta and retard important placental functions, which result in lower birth weight.
Fetal origins of adult disease-the hypothesis revisited
BMJ. 1999 Jul 24;319(7204):245-9.
- The hypothesis that adult disease has fetal origins is plausible, but much supportive evidence is flawed by incomplete and incorrect statistical interpretation.
- When size in early life is related to later health outcomes only after adjustment for current size, it is probably the change in size between these points (postnatal centile crossing) rather than fetal biology that is implicated.
- Even when birth size is directly related to later outcome, some studies fail to explore whether this is partly or wholly explained by postnatal rather that prenatal factors.
- These considerations are critical to understanding the biology and timing of "programming," the direction of future research, and future public health interventions.
Curr Opin Obstet Gynecol. 2000 Apr;12(2):111-5.
- Recent epidemiological and experimental studies show that abnormal fetal growth can lead to serious complications, including stillbirth, perinatal morbidity and disorders extending well beyond the neonatal period. It is now clear that the intrauterine milieu is as important as genetic endowment in shaping the future health of the conceptus. Maternal characteristics such as weight, height, parity and ethnic group need to be adjusted for, and pathological factors such as smoking excluded, to establish appropriate standards and improve the distinction between what is normal and abnormal. Currently, the aetiology of growth restriction is not well understood and preventative measures are ineffective. Elective delivery remains the principal management option, which emphasizes the need for better screening techniques for the timely detection of intrauterine growth failure.
Fetal growth and long-term consequences in animal models of growth retardation
Eur J Obstet Gynecol Reprod Biol. 1998 Dec;81(2):149-56.
- Perturbations of the maternal environment involve an abnormal intrauterine milieu for the developing fetus. The altered fuel supply (depends on substrate availability, placental transport of nutrients and uteroplacental blood flow) from mother to fetus induces alterations in the development of the fetal endocrine pancreas and adaptations of the fetal metabolism to the altered intrauterine environment, resulting in intrauterine growth retardation. The alterations induced by maternal diabetes or maternal malnutrition (protein-calorie or protein deprivation) have consequences for the offspring, persisting into adulthood and into the next generation.