Zusammenfassung
Leben ist grundsätzlich ein permanent umweltabhängiger Entwicklungsprozess. Sogar die Genexpressivität kann (auch sequenzunabhängig) durch Umwelteinflüsse dauerhaft modifiziert werden (Epigenomik). Derartige Gen-Umwelt-Interaktionen haben während prä- und neonataler, kritischer Entwicklungsphasen offenbar besonders nachhaltige, dauerhafte Konsequenzen für das langfristige, individuelle Erkrankungsrisiko. Mechanistisch scheint es sich hierbei um einen prinzipiell normativen, vegetativen Konditionierungsprozess zu handeln („vegetative Prägung“), bei dem epigenomisch und mikrostrukturell durch die Quantität und die Qualität von umweltabhängigen Entwicklungssignalen (Ernährung, Hormone, Xenobiotika etc.) Funktionsweisen von der subzellulären bis hin zur kybernetisch regulierten, organismischen Gesamtebene „geprägt“ werden, im Sinne einer Konditionierung, v. a. von Genom und Gehirn. So können z. B. Über- und Fehlernährung während kritischer Entwicklungsphasen das Erkrankungsrisiko für Übergewicht, Adipositas, Diabetes mellitus und kardiovaskuläre Erkrankungen dauerhaft erhöhen, insbesondere infolge einer neuroendokrinen Fehlkonditionierung. Ähnliches wurde für perinatal erworbene Störungen der Stressregulation und anderer fundamentaler Lebensfunktionen beschrieben. Disstress, Disnutrition und Disruptoren (natürliche und anthropogene Xenobiotika) scheinen als fundamentale, grundsätzliche Störgrößen perinataler Prägungsprozesse wirken zu können („Disstress-Disnutrition-Hypothese“ und „3-D-Konzept perinataler Fehlprägung“). Hieraus ergeben sich für die Zukunft mannigfaltige Chancen und Herausforderungen einer genuinen, primären Prävention im Rahmen der Entwicklungsmedizin, durch das Erkennen, Vermeiden und/oder die adäquate Behandlung maternofetaler und/oder frühpostnataler Fehlexpositionen.
Abstract
Life is principally a process of permanent environment-dependent development. Developmental origins of health and diseases are particularly sustainable if shaped during critical periods in prenatal and early postnatal life. The key to the approach is an environment-dependent epigenomic and microstructural conditioning of the organism, leading to a homeostatic calibration of functional and tolerance ranges from the subcellular up to the organismic levels (vegetative imprinting). This process, in terms of a developmental vegetative “training”, serves to optimize the self-organization of an organism in order to cope with the environmental conditions during later life. It generally occurs normatively as a basic mechanism of ontogenesis. Through alterations of the prenatal and neonatal environment it may become disadvantageous or even harmful for long-term individual health. Most important and sustainable effects occur if the main regulatory instances of the organism are affected, i.e. the genome and/or the brain. For instance, perinatal overfeeding, suggesting an affluent environment, has been shown epidemiologically, clinically and experimentally to induce epigenomic and microstructural malprogramming of the hypothalamo-adipo-pancreatic system, leading to long-term increased “diabesity” risk. Similar mechanisms have been identified for conditioning of stress responsiveness and other fundamental life functions. In general, distress, disnutrition and disruptors (unfavorable xenobiotics) appear to be the fundamental risk factors of regular vegetative programming (distress-disnutrition hypothesis and 3-D concept on perinatal malimprinting), potentially leading to acquired health risks throughout later life. In the future this opens up multiple chances and challenges for a genuine, lasting, primary prevention in developmental medicine through the recognition, avoidance and/or adequate treatment of maternofetal and/or early postnatal malexposures.
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Plagemann, A. Grundlagen perinataler Prägung und Programmierung. Monatsschr Kinderheilkd 164, 91–98 (2016). https://doi.org/10.1007/s00112-015-3419-3
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DOI: https://doi.org/10.1007/s00112-015-3419-3