The trophoblast plug during early pregnancy: a deeper insight.

During the first trimester of pregnancy, foetal endovascular trophoblasts invade into maternal spiral arteries, accumulate and form plugs in the lumen of the vessels. These plugs only allow blood plasma to seep through. Hence, during the first trimester of pregnancy, a first flow of fluids through the placental intervillous space is established, resulting in a physiological oxygen gradient between mother and foetus. The trophoblast plugs block spiral arteries until the beginning of the second trimester (11-14 weeks). In parallel, uterine glands are invaded and opened by endoglandular trophoblasts towards the intervillous space of the placenta, without showing the formation of plugs (Moser et al. in Hum Reprod 25:1127-1136, 2010, Hum Reprod Oxf Engl 30:2747-2757, 2015). This enables histiotrophic nutrition of the embryo prior to onset of maternal blood flow into the placenta. Failure of these endovascular and endoglandular invasion processes may lead to miscarriage or pregnancy disorders such as intrauterine growth restriction (IUGR). After dissolution of the plugs, the onset of maternal blood flow allows maternal blood cells to enter the intervillous space and oxygen concentrations rise up. In this study, we demonstrate for the first time serial cross sections through a trophoblast plug in a first trimester placental bed specimen. Invaded and plugged arteries as well as invaded uterine glands in week 11 of gestation are visualized with specific immunohistochemical double staining techniques. We show that spiral artery plugs appear throughout the placental invasion zone and illustrate erythrocytes stowed due to trophoblast plugs. In addition, we give evidence of the presence of MMP-1 in plugs of invaded spiral arteries. The results reveal a better understanding and a closer insight into the morphological appearance of trophoblast plugs and the consequences for placental and uterine blood flow.