Zusammenfassung
Fetale Prägung beschreibt den Zusammenhang zwischen dem Einfluss exogener und endogener Faktoren in sensiblen Phasen der Fetalentwicklung und dem Zellwachstum und der Organentwicklung, letztendlich mit dem Resultat einer anhaltenden postnatalen Veränderung in Organ- und Gewebsfunktionen. Hierbei kann eine Fehlanpassung mit dem Auftreten von Erkrankungen im gesamten späteren Leben assoziiert sein. Suboptimale intrauterine Bedingungen, wie etwa maternale Fehlernährung, Hypoxie, psychischer Stress oder aber die GC(Glukokortikoid)-Exposition, können die fetale Entwicklung nachhaltig beeinflussen und sind häufig mit einer Verringerung des Geburtsgewichts assoziiert. Das mögliche Spektrum der Spätfolgen ist hierbei weit gefächert. Die antenatale Behandlung mit GC scheint mit einer geschlechtsspezifischen fetalen Wachstumsrestriktion sowie strukturellen und funktionellen Veränderungen in der Plazenta assoziiert zu sein, die potenziell die Gesundheit im späteren Leben beeinflussen können. Während bei den weiblichen Feten eine eher kontinuierliche Sensibilität gegenüber GC zu bestehen scheint, möglicherweise im Sinne einer präferentiellen Überlebensstrategie zur Sicherung der Reproduktionsfähigkeit mit Spezieserhalt, scheint bei männlichen Feten nach GC-Exposition die Plazenta zumindest temporär eine Resistenz gegenüber GC zu entwickeln. Die geschlechtsspezifische Sensibilität gegenüber GC wird vermutlich durch ein unterschiedliches GR(GC-Rezeptoren)-Verteilungsmuster, Expression und/oder Interaktion verursacht und durch die Behandlung mit GC beeinflusst. Ein verbessertes Verständnis für die plazentavermittelten Signalwege, die zur fetalen Programmierung beitragen, wird von entscheidender Bedeutung bei den Bemühungen sein, interventionelle Strategien für Risikogruppen zu entwickeln.
Abstract
Fetal programming describes the relationship between the influence of exogenous and endogenous factors in sensitive phases of fetal development and cell growth and organ development, ultimately resulting in a persistent postnatal change in organ and tissue function. Errors in this process can be associated with the appearance of diseases in later life. Suboptimal intrauterine conditions such as maternal malnutrition, hypoxia, psychological stress, or glucocorticoid (GC) exposure during pregnancy can have lasting effects on fetal development and are often associated with a reduction in birth weight. The possible spectrum of late effects is wide ranging. Antenatal GC treatment appears to be associated with gender-specific fetal growth restriction as well as structural and functional changes in the placenta that can potentially affect health later in life. While female fetuses seem to have a rather continuous sensitivity to GC, possibly in the sense of a preferential survival strategy to ensure reproductive ability with preservation of species, in male fetuses, the placenta seems to develop, at least temporarily, a resistance to GC after GC exposure. The gender-specific sensitivity to GC is probably caused by a different GR (glucocorticoid receptors) distribution pattern, expression, and/or interaction and influenced by treatment with GC. An improved understanding of the placenta-mediated signaling pathways that contribute to fetal programming will be critical in efforts to develop interventional strategies for high-risk groups.
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Teile der Arbeit stammen aus der Habilitationsschrift von Thorsten Braun: „Antenatale Glukokortikoid-Therapie, fetale Programmierung und die Rolle der Plazenta“ (2017). https://refubium.fu-berlin.de/bitstream/handle/fub188/2044/Habil_Thorsten_Braun.pdf?sequence=1&isAllowed=y.
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Tab. S1: Assoziierte Effekte der antenatalen GC-Therapie im Tiermodell und beim Menschen. (Zusammengetragen aus Braun et al. [11] und McKinlay et al. [70])
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Braun, T. Intrauterine Prägung – Konzept und Bedeutung der Plazenta. Gynäkologe 53, 416–426 (2020). https://doi.org/10.1007/s00129-020-04621-3
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DOI: https://doi.org/10.1007/s00129-020-04621-3
Schlüsselwörter
- Fetale Programmierung
- Glukokortikoide
- Lungenreifeinduktion
- Stress
- Maternofetaler Austausch
- Fetale Wachstumsrestriktion