Abstract
In humans, the defective invasion of the maternal endometrium by fetal extravillous trophoblasts (EVTs) can lead to insufficient perfusion of the placenta, resulting in pregnancy complications that can put both mother and baby at risk. To study the invasion of maternal endometrium between (W)5.5–12 weeks of gestation by EVTs, we combined fluorescence in situ hybridization, immunofluorescence and immunohistochemistry to determine the presence of (male) EVTs in the vasculature of the maternal decidua. We observed that interstitial mononuclear EVTs directly entered decidual veins and lymphatics from W5.5. This invasion of decidual veins and lymphatics occurred long before endovascular EVTs remodelled decidual spiral arteries. This unexpected early entrance of interstitial mononuclear EVTs in the maternal circulation does not seem to contribute to the materno-placental vascular connection directly, but rather to establish (and expand) the materno-fetal interface through an alternative vascular route.
Highlights
During human placental development, at the tips of the anchoring villi, cytotrophoblasts proliferate into cell columns and from there they can detach and invade the maternal decidualized endometrium and even the myometrium [1, 2]
There are several subtypes of extravillous trophoblasts (EVTs) present in the maternal decidua, depending on their localization: the interstitial mononuclear EVTs are dispersed in the decidual mesenchyme; the endovascular EVTs and intramural EVTs are both directly associated with remodeled spiral arteries and are present in their lumen and in their tunica media [3] respectively and those EVTs migrate-colonize the spiral
Combining cytochemistry (Azan staining) and immunofluorescence for the arterial-marker ACTA2, the endothelial-marker PECAM1 and the lymphatic-marker PDPN, we were able to differentiate between arteries, veins and lymphatic vessels
Summary
At the tips of the anchoring villi, cytotrophoblasts proliferate into cell columns and from there they can detach and invade the maternal decidualized endometrium (decidua) and even the myometrium [1, 2]. Those invading fetal cytotrophoblasts are known as extravillous trophoblasts (EVTs). EVTs Invade Decidual Veins and Lymphatics during First Trimester arteries in a retrograde fashion [4]; and a fourth category of ‘epithelial’ EVTs lines, together with maternal endothelial cells in a mosaic fashion, the basal plate of the maternal decidua basalis [5]. The unique vascular remodeling of the maternal decidua during pregnancy, whereby both fetal and maternal cells play complementary regulatory roles, is a fundamental process for a successful pregnancy [8, 9]
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