Human Extravillous Trophoblasts Penetrate Decidual Veins and Lymphatics before Remodeling Spiral Arteries during Early Pregnancy

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.

SIRT1 Alleviates LPS-Induced IL-1β Production by Suppressing NLRP3 Inflammasome Activation and ROS Production in Trophoblasts

“…An adequate immune system response at the maternal-fetal interface is crucial for implantation and the preliminary stages of placentation [1]. Extravillous trophoblasts are highly proliferative cells that directly invade the uterine spiral arteries through the decidual stroma, and this process increases maternal blood flow to the placenta during early pregnancy [2,3]. Pathological inflammatory conditions such as intrauterine infection cause abnormal placental development, resulting in several pregnancy-related disorders, including preeclampsia, intrauterine growth restriction d-glucose, 10 mM HEPES, 2 mM l-glutamine, and 1 mM sodium pyruvate.…”

Traditional and New Routes of Trophoblast Invasion and Their Implications for Pregnancy Diseases

“…At the same time, the remaining secretion products and the respective fluids need to be drained back into the maternal system. Hence, erosion and connection of uterine veins to the intervillous space of the placenta needs to take place next ( Figure 2A) [24][25][26]. Other images of the Enders collection show the junctional zone of trophoblast invasion at the secondary villus stage.…”

“…Following invasion into uterine glands, it seems as if the next route of invasion guides extravillous trophoblasts toward uterine veins (Figure 2A) [24][25][26]. The secretion products of the uterine glands need to be removed from the growing intervillous space.…”

The TGFβ Family in Human Placental Development at the Fetal-Maternal Interface

“…The remodelling of the spiral arteries takes place in the endometrium and can even reach the first third of the myometrium [26]. Between 5-10 WG, interstitial EVTs migrate and invade both veins and lymphatics, but do not remodel their ECs [27], as well as invading uterine glands [28]. It remains to be investigated whether EVTs enter the maternal circulation and will trigger the maternal immune system to promote immune tolerance.…”