In the first trimester of human pregnancy villous cytotrophoblasts are able to differentiate to form either the overlying syncytiotrophoblast layer or, in anchoring villi, extravillous trophoblasts which grow out from the villi and invade into the maternal decidua, acting to both physically attach the placenta to the decidua, and modify the maternal spiral arteries to sustain pregnancy. During the first 10–12 weeks of gestation, extravillous trophoblast plugs block the spiral arteries and prevent maternal blood flow entering the intervillous space, thereby creating an environment of physiological hypoxia in which placental and fetal development occur. As extravillous trophoblasts migrate away from the villus they differentiate from a proliferative to an invasive phenotype. The hypoxic environment of the first trimester is believed to play an important role in the regulation of trophoblast differentiation. However, there is currently a large body of conflicting experimental evidence concerning this topic. This review examines the experimental evidence to date on the role of oxygen in trophoblast differentiation.

Introduction: Recent studies have demonstrated an association between maternal supine sleep position and an increased risk of late stillbirth. During late pregnancy, the gravid uterus compresses the inferior vena cava (IVC) when a woman lies in the supine position. The azygos system of veins is the dominant pathway of collateral venous return back to the heart in the event of acute obstruction of the IVC. It is suggested that this pathway provides adequate collateral venous circulation in the event of IVC compression in the supine position during late pregnancy. Objective: Investigate the effect of supine positioning on maternal hemodynamics during late pregnancy and the role of collateral venous circulation. Methods: Ethics approval was obtained and 12 women with singleton pregnancies between 35- and 38-week gestation underwent magnetic resonance imaging in the supine and left lateral decubitus positions using a Skyra 3T system (Siemens). Phase-contrast images were evaluated to measure cardiac output, blood flow through the azygos vein, and blood flow through the abdominal aorta (AA) and IVC at two levels: at the level of aortic bifurcation and immediately above the renal veins. Results: The supine position was associated with a 16.4% reduction in cardiac output when compared to the left lateral position. In addition, blood flow through the IVC decreased at its origin by 85.3% and by 44.4% at the level of the renal veins. Blood flow through the azygos vein increased in the supine position by 220%. Blood flow through the AA at the level of the renal veins did not differ significantly; however, it is reduced by 32.3% at the level of the aortic bifurcation. Conclusions: Women in late pregnancy experience an increase in collateral venous blood flow when lying supine, likely as a response to marked compression of the IVC in this position. However, cardiac output and aortic blood flow were found to decrease while in the supine position.

Sleep disturbances in late pregnancy are common. This study aimed to survey sleep problems in third trimester pregnant women and to compare sleep in the pre-pregnancy period with the third trimester.

It is commonly accepted that a single pool of villous cytotrophoblasts are precursors of both syncytiotrophoblast and extravillous trophoblasts during the first trimester. Here we present evidence that these two trophoblast subpopulations arise from separate progenitors that have different survival characteristics when studied in villous explant cultures. Dual staining with chloromethylfluorescin diacetate and ethidium bromide revealed degeneration of the syncytiotrophoblast by non-apoptotic mechanisms within 4 h of culture. The syncytiotrophoblast had regenerated within 48 h but at this point the vast majority of the cytotrophoblast and cells of the mesenchymal core were dead. Despite this extensive cytotrophoblast death, explants are able to produce extravillous trophoblast outgrowth for up to 3 weeks in culture. We believe that the villous cytotrophoblasts in the tips of anchoring villi are resistant to the factors that cause the death of the majority of villous cytotrophoblasts in culture. We speculate that as early as 8 weeks of gestation there are two separate villous cytotrophoblast populations, one committed to differentiate into syncytiotrophoblast and the second committed to the extravillous differentiation pathway

It is hypothesized that preeclampsia is caused by factors from the placenta that induce endothelial cell activation. Trophoblasts are cells that may be shed from the placenta, then deported in the maternal blood, and finally become trapped in the pulmonary capillaries. The ultimate fate of deported trophoblasts is unknown, but to prevent clogging of the pulmonary circulation they must be cleared from the capillary beds. We examined the hypothesis that endothelial cells phagocytose deported trophoblasts and also examined the consequent effects of the trophoblasts on endothelial cells. Fluorescently labeled trophoblast–derived choriocarcinoma cells were induced to become apoptotic or necrotic and exposed to endothelial cell monolayers. Confocal microscopy demonstrated uptake of both apoptotic and necrotic trophoblasts, and this phagocytosis could be inhibited by cytochalasin B. Phagocytosis of necrotic but not apoptotic trophoblasts induced increased endothelial intercellular adhesion molecule 1 (ICAM-1) expression, as well as increased adhesion of monocytes to endothelial cell monolayers. Inhibiting the phosphatidylinositol 3-kinase and p38 mitogen-activated protein kinase pathways blocked both expression of ICAM-1 and phagocytosis, whereas inhibition of the P42/44 mitogen-activated protein kinase pathway blocked only ICAM-1 expression. This work suggests that endothelial cells can phagocytose deported trophoblasts and that the mechanism of trophoblast death (apoptotic or necrotic) could have major effects on the maternal vascular response to shed trophoblasts.