Mütterlich-plazentare Interaktionen und fetale Programmierung

Zusammenfassung

Schwangerschaftskomplikationen führen nicht nur zu einer erhöhten maternalen und fetalen Morbidität und Mortalität, sie erhöhen auch das Risiko für Erkrankungen im späteren Leben. Viele epidemiologische Studien haben eine klare Assoziation zwischen einem ungünstigen intrauterinen Umfeld und einem erhöhten Risiko für Diabetes, Hypertension und kardiovaskuläre Erkrankungen, Depression, Adipositas und andere chronische Erkrankungen bei Erwachsenen gezeigt. Einige dieser Erkrankungen könnten verhindern werden, wenn ungünstige Stimuli während der Schwangerschaft vermieden würden wie psychosozialer Stress, Einnahme von Drogen, unausgewogene Ernährung und ungünstige Arbeitsbedingungen. Diese Stimuli haben das Potenzial, die Gesundheit im späteren Leben nachhaltig zu beeinflussen. Die Plazenta spielt eine Schlüsselrolle bei der Regulation der Nahrungsversorgung des Feten und produziert Hormone, die sowohl den fetalen als auch den maternalen Metabolismus kontrollieren. Daher wird jeder Faktor oder Stimulus, der die Funktion des Hormon-produzierenden plazentaren Trophoblasten verändert, kritische Veränderungen der plazentaren Funktion mit sich bringen und damit eine fetale Programmierung induzieren können. Die Faktoren, die die plazentare Entwicklung beeinflussen, können zu einer Behinderung der Versorgung des Feten mit Sauerstoff und Nährstoffen führen, entweder über eine direkte Störung der Plazentaschranke oder indirekt über eine Störung der Trophoblastinvasion. Für beide Wege sind entsprechende Pathologien beschrieben worden: Bei der Präeklampsie liegt die Störung beim villösen Trophoblasten, der Plazentaschranke, während bei einer intrauterinen Wachstumsrestriktion der Grund in einer Mangelinvasion des Trophoblasten liegt. In beiden Fällen kann die Konsequenz Unterernährung und/oder Hypoxie des Feten sein und damit eine negative Beeinflussung der fetalen Organ­entwicklung, vor allem von Herz und Hirn. Allerdings ist bis heute unklar, welche Mechanismen für die Störungen von Trophoblastdifferenzierung und -funktion verantwortlich sind.

Abstract

Pregnancy-related complications not only represent a risk for maternal and fetal morbidity and mortality, but are also a risk for several diseases later in life. Many epidemiological studies have shown clear associations between an adverse intrauterine environment and an increased risk of diabetes, hypertension, cardiovascular disease, depression, obesity, and other chronic diseases in the adult. Some of these syndromes could be prevented by avoiding adverse stimuli or insults including psychological stress during pregnancy, intake of drugs, insufficient diet and substandard working conditions. Hence, all of these stimuli have the potential to alter health later in life. The placenta plays a key role in regulating the nutrient supply to the fetus and producing hormones that control the fetal as well as the maternal metabolism. Thus, any factor or stimulus that alters the function of the hormone producing placental trophoblast will provoke critical alterations of placental function and hence could induce programming of the fetus. The factors that change placental development may inter­fere with nutrient and oxygen supply to the fetus. This may be achieved by a direct disturbance of the placental barrier or more indirectly by, e. g., disturbing trophoblast invasion. For both path­ways, the respective pathologies are known: while preeclampsia is caused by alterations of the villous trophoblast, intra-uterine growth restriction is caused by insufficient invasion of the extravillous trophoblast. In both cases the effect can be undernutrition and/or fetal hypoxia, both of which adversely affect organ development, especially of brain and heart. However, the mechanisms responsible for disturbances of trophoblast differentiation and function remain elusive.

Schlüsselwörter

fetale Programmierung - Plazenta - Trophoblast-Invasion

Key words

fetal programming - placenta - trophoblast invasion

^* Beide Autoren haben zu gleichen Teilen zu dieser Arbeit beigetragen.

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