Fetal origins of adult disease-the hypothesis revisited.
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ABSTRACT:
SUBMITTER: Lucas A
PROVIDER: S-EPMC1116334 | biostudies-literature | 1999 Jul
REPOSITORIES: biostudies-literature
Publications
Fetal origins of adult disease-the hypothesis revisited.
Lucas A A Fewtrell M S MS Cole T J TJ
BMJ (Clinical research ed.) 19990701 7204
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Project description:Birth weight is a robust predictor of valued life course outcomes, emphasizing the importance of prenatal development. But does birth weight act as a proxy for environmental conditions in utero, or do biological processes surrounding birth weight themselves play a role in healthy development? To answer this question, we leverage variation in birth weight that is, within families, orthogonal to prenatal environmental conditions: one's genes. We construct polygenic scores in two longitudinal studies (Born in Bradford, N = 2008; Wisconsin Longitudinal Study, N = 8488) to empirically explore the molecular genetic correlates of birth weight. A 1 standard deviation increase in the polygenic score is associated with an ~100-grams increase in birth weight and a 1.4 pp (22 percent) decrease in low birth weight probability. Sibling comparisons illustrate that this association largely represents a causal effect. The polygenic score-birth weight association is increased for children who spend longer in the womb and whose mothers have higher body mass index, though we find no differences across maternal socioeconomic status. Finally, the polygenic score affects social and cognitive outcomes, suggesting that birth weight is itself related to healthy prenatal development.
| S-EPMC11021852 | biostudies-literature
Project description:In uncomplicated pregnancies, birthweight is inversely associated with adult non-communicable disease (NCD) risk. One proposed mechanism is maternal malnutrition during pregnancy. Another explanation is that shared genes link birthweight with NCDs. Both hypotheses are supported, but evolutionary perspectives address only the environmental pathway. We propose that genetic and environmental associations of birthweight with NCD risk reflect coordinated regulatory systems between mother and foetus, that evolved to reduce risks of obstructed labour. First, the foetus must tailor its growth to maternal metabolic signals, as it cannot predict the size of the birth canal from its own genome. Second, we predict that maternal alleles that promote placental nutrient supply have been selected to constrain foetal growth and gestation length when fetally expressed. Conversely, maternal alleles that increase birth canal size have been selected to promote foetal growth and gestation when fetally expressed. Evidence supports these hypotheses. These regulatory mechanisms may have undergone powerful selection as hominin neonates evolved larger size and encephalisation, since every mother is at risk of gestating a baby excessively for her pelvis. Our perspective can explain the inverse association of birthweight with NCD risk across most of the birthweight range: any constraint of birthweight, through plastic or genetic mechanisms, may reduce the capacity for homeostasis and increase NCD susceptibility. However, maternal obesity and diabetes can overwhelm this coordination system, challenging vaginal delivery while increasing offspring NCD risk. We argue that selection on viable vaginal delivery played an over-arching role in shaping the association of birthweight with NCD risk.
| S-EPMC10878253 | biostudies-literature
Project description:ObjectiveTo assess the direct and indirect effects of being a twin, maternal smoking, birth weight, and mother's height on blood pressure at ages 9 and 18 years.DesignLongitudinal study.SubjectsCohort born in 1972-3.SettingDunedin, New Zealand.Main outcome measureBlood pressure at ages 9 and 18 years.ResultsCompared with singletons, twins had a systolic blood pressure 4.55 (95% confidence interval 1.57 to 7.52) mm Hg lower at age 9 after adjustment for direct and indirect effects of sex, maternal smoking, mother's height, socioeconomic status, and birth weight, as well as concurrent height and body mass index. Blood pressure in children whose mothers had smoked during pregnancy was 1.54 (0.46 to 2.62) mm Hg higher than in those whose mothers did not. The total effect of birth weight on systolic blood pressure at age 9 was -0.78 (-1.76 to 0.20) mm Hg and that for mother's height was 0.10 (0.06 to 0.14) mm Hg. Similar results were obtained for systolic blood pressure at age 18. The total effect of twins, maternal smoking, and birth weight on diastolic blood pressure was not significant at either age.ConclusionsTwins had lower birth weight and lower systolic blood pressure at ages 9 and 18 than singletons. This finding challenges the fetal origins hypothesis. The effect of maternal smoking was consistent with the fetal origin hypothesis in that the infants of smokers were smaller and had higher blood pressure at both ages. This may be explained by pharmacological rather than nutritional effects. The total effect of birth weight on systolic blood pressure, after its indirect effect working through concurrent measures of height and body mass index was taken into account, was small.
| S-EPMC27807 | biostudies-literature
Project description:In the ongoing research of the functions of consciousness, special emphasis has been put on integration of information: the ability to combine different signals into a coherent, unified one. Several theories of consciousness hold that this ability depends on - or at least goes hand in hand with - conscious processing. Yet some empirical findings have suggested otherwise, claiming that integration of information could take place even without awareness. Trying to reconcile this apparent contradiction, the "windows of integration" (WOI) hypothesis claims that conscious access enables signal processing over large integration windows. The hypothesis applies to integration windows defined either temporally, spatially, or semantically. In this review, we explain the hypothesis and re-examine it in light of new studies published since it was suggested. In line with the hypothesis, these studies provide compelling evidence for unconscious integration, but also demonstrate its limits with respect to time, space, and semantic distance. The review further highlights open questions that still need to be pursued to demonstrate the applicability of the WOI hypothesis as a guiding principle for understanding the depth and scope of unconscious processes.
| S-EPMC7840615 | biostudies-literature
Project description:The Centers for Disease Control and Prevention estimate that 1 in 323 infants have cerebral palsy. Highly correlated to intrauterine infection and inflammation, the incidence of cerebral palsy has remained constant over the last few decades despite significant advances in neonatal intensive care including improved ventilator techniques, surfactant therapy, maternal steroid administration, and use of intrapartum empiric antimicrobials. Recent advances in our understanding of immune responses to infection and inflammation have identified the cytokine IL-17A as a crucial component of early proinflammatory mediators that cause brain injury associated with neurologic impairment. Remarkably, maternal inflammatory responses to in utero inflammation and infection can also lead to potentially debilitating neurologic conditions in the offspring, which often become clinically apparent during childhood and/or early adulthood. This review details the role of IL-17A in fetal and maternal proinflammatory responses that lead to fetal brain injury and neurologic sequelae, including cerebral palsy. Recent findings regarding the role of maternal inflammatory responses in the development of childhood and adult neurologic conditions, such as autism, schizophrenia, and multiple sclerosis, will also be highlighted.
| S-EPMC5966827 | biostudies-literature
Project description:Elevated levels of inflammatory mediators have been identified in patients with heart failure, including heart failure with reduced and preserved ejection fraction, as well as acute decompensated heart failure. Moreover, experimental studies have shown repeatedly that activation of inflammation in the heart provokes left ventricular remodeling and left ventricular dysfunction. Nonetheless, phase III clinical trials that have attempted to antagonize inflammatory mediators have been negative with respect to the primary end points of the trials, and in some patients, resulted in worsening heart failure or death. The following review will discuss how recent developments in the field of innate immunity have advanced our understanding of the role of inflammation in the pathogenesis of heart failure and will discuss the negative outcomes of the existing clinical trials in light of this new information.
| S-EPMC4380242 | biostudies-literature
Project description:The Barker hypothesis strongly supported the influence of fetal environment on the development of chronic diseases in later life. Multiple experimental and human studies have identified that the deleterious effect of fetal programming commonly leads to alterations in renal development. The interplay between environmental insults and fetal genome can induce epigenetic changes and lead to alterations in the expression of renal phenotype. In this review, we have explored the renal development and its functions, while focusing on the epigenetic findings and functional aspects of the renin-angiotensin system and its components.
| S-EPMC7546361 | biostudies-literature
Project description:BackgroundChronic obstructive pulmonary disease (COPD) is a leading cause of death in adults that may have origins in early lung development. It is a complex disease, influenced by multiple factors including genetic variants and environmental factors. Maternal smoking during pregnancy may influence the risk for diseases during adulthood, potentially through epigenetic modifications including methylation.MethodsIn this work, we explore the fetal origins of COPD by utilizing lung DNA methylation marks associated with in utero smoke (IUS) exposure, and evaluate the network relationships between methylomic and transcriptomic signatures associated with adult lung tissue from former smokers with and without COPD. To identify potential pathobiological mechanisms that may link fetal lung, smoke exposure and adult lung disease, we study the interactions (physical and functional) of identified genes using protein-protein interaction networks.ResultsWe build IUS-exposure and COPD modules, which identify connected subnetworks linking fetal lung smoke exposure to adult COPD. Studying the relationships and connectivity among the different modules for fetal smoke exposure and adult COPD, we identify enriched pathways, including the AGE-RAGE and focal adhesion pathways.ConclusionsThe modules identified in our analysis add new and potentially important insights to understanding the early life molecular perturbations related to the pathogenesis of COPD. We identify AGE-RAGE and focal adhesion as two biologically plausible pathways that may reveal lung developmental contributions to COPD. We were not only able to identify meaningful modules but were also able to study interconnections between smoke exposure and lung disease, augmenting our knowledge about the fetal origins of COPD.
| S-EPMC8944072 | biostudies-literature
Project description:The relationship between Scleractinia and Corallimorpharia, Orders within Anthozoa distinguished by the presence of an aragonite skeleton in the former, is controversial. Although classically considered distinct groups, some phylogenetic analyses have placed the Corallimorpharia within a larger Scleractinia/Corallimorpharia clade, leading to the suggestion that the Corallimorpharia are "naked corals" that arose via skeleton loss during the Cretaceous from a Scleractinian ancestor. Scleractinian paraphyly is, however, contradicted by a number of recent phylogenetic studies based on mt nucleotide (nt) sequence data. Whereas the "naked coral" hypothesis was based on analysis of the sequences of proteins encoded by a relatively small number of mt genomes, here a much-expanded dataset was used to reinvestigate hexacorallian phylogeny. The initial observation was that, whereas analyses based on nt data support scleractinian monophyly, those based on amino acid (aa) data support the "naked coral" hypothesis, irrespective of the method and with very strong support. To better understand the bases of these contrasting results, the effects of systematic errors were examined. Compared to other hexacorallians, the mt genomes of "Robust" corals have a higher (A+T) content, codon usage is far more constrained, and the proteins that they encode have a markedly higher phenylalanine content, leading us to suggest that mt DNA repair may be impaired in this lineage. Thus the "naked coral" topology could be caused by high levels of saturation in these mitochondrial sequences, long-branch effects or model violations. The equivocal results of these extensive analyses highlight the fundamental problems of basing coral phylogeny on mitochondrial sequence data.
| S-EPMC3989238 | biostudies-literature
Project description:Walter (Jahrb Wiss Bot 87:750-860, 1939) proposed a two-layer hypothesis, an equilibrium explanation for coexistence of savanna trees and grasses. This hypothesis relies on vertical niche partitioning and assumed that grasses are more water-use efficient than trees and use subsurface water while trees also have access to deeper water sources. Thus, in open savannas, grasses were predicted to predominate because of their water use efficiency and access to subsurface water. This hypothesis has been a prominent part of the savanna literature since first proposed. We review the literature on Walter's hypothesis and reconsider his original intentions. Walter intended this hypothesis to be restricted to dry savannas. In his opinion, mesic and humid savannas were controlled by biotic factors and disturbances. We surveyed the global savanna literature for records of vertical niche partitioning by grasses and trees. We find that, within the scope of Walter's original intentions, this hypothesis works remarkably well, and in some cases is appropriate for deserts as well as for dry temperate systems and even some mesic savannas.
| S-EPMC3679411 | biostudies-other