Studies of Placental Vasculogenesis: a Way to Understand Pregnancy Pathology?[*]

Abstract

Undisturbed development and growth of the fetus depends on an adequate vascular development in the fetomaternal unit. Several steps of vascular adaptation both on fetal and maternal side are necessary and involve uterine vasodilation and remodelling by extravillous trophoblast as well as vasculo- and angiogenesis within the placenta. Ubiquitous (e. g. VEGF, bFGF) as well as pregnancy specific (PlGF, hCG, IGF-II, AFP) angiogenic factors are involved. Consequences of abnormal vascular development have been associated with different pregnancy-related pathologies ranging from miscarriage to intrauterine growth restriction or preeclampsia. Pregnancy-associated exposure to bacterial and viral infections or toxic agents (e. g. alcohol, nicotine or drugs) may also influence vascular development of the placenta and often lead to preterm labour and delivery. Different methods of study placental vascular development exist. Morphological and stereological approaches as well as animal models reveal significant limitations and can not be applied to in vivo human situation without hesitation. There is a need to design in vitro models of human placental vascular development allowing studies into the different aspects of this process including: trophoblast and stromal cells, interaction with endothelial progenitor cells, influence of viral or bacterial infection of trophoblast as well as influence of toxic agents. Our manuscript reviews major aspects of vascular development in the placenta and describes author's efforts to establish a three-dimensional model of this process in vitro.

Zusammenfassung

Eine normale Entwicklung und ein regelrechtes Wachstum des Feten hängen von einer adäquaten vaskulären Entwicklung in der fetomaternalen Einheit ab. Eine Vielzahl dieser Schritte sowohl auf der fetalen als auch auf der maternalen Seite ist erforderlich und umfasst die uterine Vasodilatation, die Trophoblasten-Invasion in uterine Gefäße, sowie die adäquate Vaskulo- und Angiogenese in der Plazenta selbst. Sowohl ubiquitäre (VEGF, bFGF) als auch schwangerschafts-spezifische Angiogenesefaktoren (hCG, IGF-II, AFP) sind daran beteiligt. Konsequenzen von vaskulären Abnormalitäten können zu verschiedenen schwangerschafts-spezifischen Pathologien führen, die von Fehlgeburten bis hin zu intrauteriner Wachstumsrestriktion oder Präeklampsie reichen. Expositionen gegenüber bakteriellen oder viralen Infektionen, sowie toxischen Substanzen (Alkohol, Nikotin, Drogen) im Schwangerschaftsverlauf können die Gefäßentwicklung der Plazenta beeinflussen und zu Komplikationen führen. In der Vergangenheit wurden zahlreiche Untersuchungsmethoden der plazentaren Gefäßentwicklung beschrieben. Morphologische und stereologische Studien sowie einige tierexperimentelle Ansätze weisen Grenzen auf und können nicht vorbehaltlos auf den Menschen übertragen werden. Es besteht deshalb Bedarf in vitro Modelle zur humanen plazentaren Gefäßentwicklung zu entwerfen, die Studien über die verschiedenen Aspekte dieses Prozesses erlauben und folgende Themen adressieren: Trophoblast und Stromazellen, Interaktion mit endothelialen Progenitorzellen, Einfluss von Viren und Bakterien auf den Trophoblasten, sowie Auswirkungen von Alkohol, Nikotin und Drogen. Der vergleichende entwicklungsbiologische Ansatz geht auf die methodischen Aspekte der plazentaren Gefäßentwicklung ein und fasst eigene Erfahrungen der Autoren in diesem Forschungsfeld zusammen.

Key words

vasculogenesis - human placenta - in vitro model

Schlüsselwörter

Vaskulogenese - Plazenta - in vitro Modell

1 This review was presented at the Perinatal Society Meeting in Bonn, 2008.

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1 This review was presented at the Perinatal Society Meeting in Bonn, 2008.

Correspondence