Figure 8. Effects of placental sFlt1 knockdown with or without endometrial VEGF overexpression. (A-L) Placental sFlt1 knockdown. Upon placentaspecific sFLT1 shRNA expression, widespread hemorrhaging in the fetus (B) and at the placental-decidual junction (D) was observed on GD18 compared with controls (A and C). Histological examination of sFLT1 shRNA-expressing placentas revealed extraordinary dilation of some maternal blood sinuses (arrowheads) in the labyrinth (E and F) and fibrin deposition (arrow) in these spaces (G and H). (I and J) MSB staining revealed extravasated fibrin (arrow) in adjacent areas. Placental sFlt1 knockdown did not affect implantation rate (K), whereas the fetal resorption rate significantly increased (L). (M-V) Placental sFlt1 knockdown enhanced the deleterious effects in Endo-VEGF animals. Pregnancies surviving to GD16 exhibited (M) excessive vaginal bleeding and (N-P) termination of pregnancy or resorption (arrows denote resorption sites) as well as (Q) widespread and extensive hemorrhaging in fetuses and placentas (arrowheads) and in deciduas at the maternal-fetal junction (asterisk). Histological examination (R-T) revealed widespread dilation and congestion of maternal blood sinuses (arrowheads) in the labyrinth, venous sinuses, and veins at maternal-fetal junctions, and MSB staining (U and V) demonstrated extensive fibrin extravasation (arrows) in the labyrinth and at the maternal-fetal junction. Results are mean ± SD. *P < 0.05 (n = 15). Scale bars: 2 mm (A-D); 500 μm (E, F, and R); 50 μm (G-J); 100 μm (S-V).

The maternal vasculature within the placenta in primates and rodents is unique because it is lined by fetal cells of the trophoblast lineage and not by maternal endothelial cells. In addition to trophoblast cells that invade the uterine spiral arteries that bring blood into the placenta, other trophoblast subtypes sit at different levels of the vascular space. In mice, at least five distinct subtypes of trophoblast cells have been identified which engage maternal endothelial cells on the arterial and venous frontiers of the placenta, but which also form the channel-like spaces within it through a process analogous to formation of blood vessels (vasculogenic mimicry). These cells are all large, post-mitotic trophoblast giant cells. In addition to assuming endothelial cell-like characteristics (endothelial mimicry), they produce dozens of different hormones that are thought to regulate local and systemic maternal adaptations to pregnancy. Recent work has identified distinct molecular pathways in mice that regulate the morphogenesis of trophoblast cells on the arterial and venous sides of the vascular circuit that may be analogous to specification of arterial and venous endothelial cells.

The maternal blood space in the mouse placenta is lined not by endothelial cells but rather by various subtypes of trophoblast giant cells (TGCs), defined by their location and different patterns of gene expression. While TGCs invade the spiral arteries to displace the maternal endothelium, the rest of the vascular space is created de novo but the mechanisms are not well understood. We cultured mouse trophoblast stem (TS) cells in suspension and found that they readily form spheroids (trophospheres). Compared to cells grown in monolayer, differentiating trophospheres showed accelerated expression of TGC-specific genes. Morphological and gene expression studies showed that cavities form within the trophospheres that are primarily lined by Prl3d1/Pl1α-positive cells analogous to parietal-TGCs (P-TGCs) which line the maternal venous blood within the placenta. Lumen formation in trophospheres and in vivo was associated with cell polarization including CD34 sialomucin deposition on the apical side and cytoskeletal rearrangement. While P-TGCs preferentially formed in trophospheres at atmospheric oxygen levels (19%), decreasing oxygen to 3% shifted differentiation towards Ctsq-positive sinusoidal and/or channel TGCs. These studies show that trophoblast cells have the intrinsic ability to form vascular channels in ways analogous to endothelial cells. The trophosphere system will be valuable for assessing mechanisms that regulate specification of different TGC subtypes and their morphogenesis into vascular spaces.

INTRODUCTIONHaemangioma of ovary is a rare tumour.PRESENTATION OF CASEWe report an ovarian haemangioma which presented as an acute abdomen due to an adnexal mass.DISCUSSIONWe report an ovarian haemangioma which presented as an acute abdomen due to an adnexal mass. Haemangiomas have been reported in other organs but ovarian haemangioma is a rare tumor, usually asymptomatic and presenting as an incidental finding. Large lesions tend to present clinically with pain. A few cases have been described in the literature.CONCLUSIONConsidering their rare occurrence such tumors are a diagnostic challenge.

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