Experimental studies regarding coronary embryogenesis suggest that the endocardium is a source of endothelial cells for the myocardial networks. As this was not previously documented in human embryos, we aimed to study whether or not endothelial tip cells could be correlated with endocardial-dependent mechanisms of sprouting angiogenesis. Six human embryos (43–56 days) were obtained and processed in accordance with ethical regulations; immunohistochemistry was performed for CD105 (endoglin), CD31, CD34, α-smooth muscle actin, desmin and vimentin antibodies. Primitive main vessels were found deriving from both the sinus venosus and aorta, and were sought to be the primordia of the venous and arterial ends of cardiac microcirculation. Subepicardial vessels were found branching into the outer ventricular myocardium, with a pattern of recruiting α-SMA+/desmin+ vascular smooth muscle cells and pericytes. Endothelial sprouts were guided by CD31+/CD34+/CD105+/vimentin+ endothelial tip cells. Within the inner myocardium, we found endothelial networks rooted from endocardium, guided by filopodia-projecting CD31+/CD34+/CD105+/ vimentin+ endocardial tip cells. The myocardial microcirculatory bed in the atria was mostly originated from endocardium, as well. Nevertheless, endocardial tip cells were also found in cardiac cushions, but they were not related to cushion endothelial networks. A general anatomical pattern of cardiac microvascular embryogenesis was thus hypothesized; the arterial and venous ends being linked, respectively, to the aorta and sinus venosus. Further elongation of the vessels may be related to the epicardium and subepicardial stroma and the intramyocardial network, depending on either endothelial and endocardial filopodia-guided tip cells in ventricles, or mostly on endocardium, in atria.

Interstitial cells of Cajal (ICCs) are located in various smooth muscle organs and act as pacemaker cells, or ensure neuromodulation or mechanosensory roles. The study aims to investigate functional states of human ICCs in morphogenesis, focusing on the anoctamin 1 phenotype. The investigation was performed in five late stage human embryos with lengths varying between 23 and 29 mm. Immunohistochemistry on paraffin embedded specimens was performed for a series of antibodies: a-smooth muscle actin (a-SMA), desmin, CD31, CD34, CD117/c-kit, DOG1, and nestin. Longitudinal and circular muscle layers were a-SMA1/desmin1/nestin1. An immature microvascular layer located in the inner submucosa was CD341/CD311/a-SMA1/ nestin1; endothelial tip cells were supporting active processes of sprouting angiogenesis. A CD341/CD31-mesenchymal network was found in the circular muscle layer. CD117/c-kit1 multipolar ICCs with dichotomizing processes were found mostly in the myenteric plexus layer; processes were configuring a network within the circular muscle layer where intramuscular ICCs were scarcely found. A strong DOG11 reaction was found for the ICCs of the myenteric plexus layer apposed on the outer surface of the circular muscle layer, and for the intramuscular ICCs.

The etiology of fetal limb abnormalities is very complex, involving different risk factors: chromosomal abnormalities, gene disorders, intrauterine factors, maternal diseases, or exposure to different risk factors. The prevalence of fetal limb anomalies is reported to be approximately 6 in 10,000 live births, and the impairments of the upper limbs seem to present a higher incidence in comparison to the inferior limbs, more often are affected unilaterally and on the right side in comparison to the left side, some being isolate or may associate other anomalies, as a part of an underlying syndrome. According to the current guidelines, the assessment of the fetal limbs should be performed in the late first and early second trimester. Three-dimensional ultrasound provides a better understanding of the fetal anomaly for the parents and helps a better counseling, and it is used to confirm the anomalies detected by the conventional ultrasound. In cases of treatable anomalies, a multidisciplinary approach involving an obstetrician, geneticist, neonatologist, pediatrician, and pediatric orthopedic surgeon is essential to improve the postnatal outcome. Ultrasound examination and genetic counseling for the parents has an important benefit since some conditions present a genetic inheritance, and the recurrence rate in further pregnancies is very high.

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by clinical manifestations caused by arterial or venous thrombosis and pregnancy conditions such as recurrent miscarriage, fetal death, or premature birth in the presence of antiphospholipid antibodies. The obstetrical manifestations are strongly related to the placental alterations. The aim of this review is to summarize the latest data on pathophysiology of obstetrical APS, emphasizing the disturbance of the placentation process. Due to a lack of extravillous trophoblasts to properly reconstruct the spiral arteries, APS causes hypoxic or ischemic injury or high-speed blood flow that damages the placenta. This results in decreased or interrupted maternal blood flow to the placenta and a lack of nutrients for the fetus. Antiphospholipid antibodies can lower the proliferation and infiltration of the extravillous trophoblasts. The placental mal-perfusion causes the release of antiangiogenic substances such as soluble fms-like tyrosine kinase-1 and soluble endoglin. Placental growth factor and vascular endothelial growth factor (VEGF) may be sequestered by sFlt1 and blocked from binding to trophoblast and endothelial cell VEGF receptors, inhibiting their proangiogenic effects. Preeclampsia is the clinical result from a lack of angiogenic factors needed for endothelial vascular homeostasis due to an excess of sFlt1 in the maternal circulation.