Extravillous trophoblasts invade more than uterine arteries: evidence for the invasion of uterine veins

Abstract

During the first trimester of pregnancy, extravillous trophoblasts (EVTs) invade into the decidual interstitium to the first third of the myometrium, thereby anchoring the placenta to the uterus. They also follow the endovascular and endoglandular route of invasion; plug, line and remodel spiral arteries, thus being responsible for the establishment of hemotrophic nutrition with the beginning of the second trimester and invade and open uterine glands toward the intervillous space for a histiotrophic nutrition during the first trimester. The aim of this study was to provide proof that uterine veins are invaded by EVTs similar to uterine arteries and glands in first trimester of pregnancy. Therefore, serial sections from in situ first trimester placenta were immuno-single- and immuno-double-stained to distinguish in a first step between arteries and veins and secondly between invaded and non-invaded vessels. Subsequently, invasion of EVTs into uterine vessels was quantified. Our data show that uterine veins are significantly more invaded by EVTs than uterine arteries (29.2 ± 15.7 %) during early pregnancy. Counted vessel cross sections revealed significantly higher EVT invasion into veins (59.5 ± 7.9 %) compared to arteries (29.2 ± 15.7 %). In the lumen of veins, single EVTs were repeatedly found, beside detached glandular epithelial cells or syncytial fragments. This study allows the expansion of our hitherto postulated concept of EVT invasion during first trimester of pregnancy. We suggest that invasion of EVTs into uterine veins is responsible the draining of waste and blood plasma from the intervillous space during the first trimester of pregnancy.

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

“…Consistent with our findings, very recently the group of Huppertz has also showed evidence for EVTs invasion of uterine veins [29], using an antibody against human leukocyte antigen (HLA)-G, often used as specific EVT marker [30]. However, caution should be taken when using only HLA-G to identify EVTs, due to the different HLA-G isoforms [31].…”

“…However, caution should be taken when using only HLA-G to identify EVTs, due to the different HLA-G isoforms [31]. In addition, using HLA-G immunostaining as means to identify EVTs, the same group has also reported that EVTs (coined “endoglandular”) also invaded uterine glands [29, 32, 33]. In our study, using a combination of immunofluorescence and FISH, we were unable to detect (male) EVTs in maternal uterine glands between W5.5 and W12.…”

Early missed abortion is associated with villous angiogenesis via the HIF-1α/VEGF signaling pathway

“…Remodeling of maternal spiral arteries involves trophoblast invasion and EVT differentiation, whereby EVT forms the linings of the uterine vessels [2]. Spiral arterioles are blocked by invading endovascular trophoblasts that restrict blood flow and thereby sustain a low oxygen environment of 1–2% oxygen.…”

Fetal Cells in Maternal Blood For Prenatal Diagnosis: A Love Story Rekindled

“…In the placenta, some cytotrophoblasts from the column of the anchoring villi invade the maternal decidua [21]. Eventually we know that these invading trophoblasts line the spiral arteries, glands and veins and could be the source of fetal cells in maternal circulation [22]. This method of targeting EVTs has been very reliable in enriching fetal cells from every pregnant sample.…”