Abstract
ABSTRACTHuman placental architecture is complex. Its surface epithelium, specialized for transport, forms by fusion of cytotrophoblast progenitors into multinucleated syncytiotrophoblasts. Near the uterine surface, these progenitors assume a different fate, becoming cancer-like cells that invade its lining and blood vessels. The latter process physically connects the placenta to the mother and shunts uterine blood to the syncytiotrophoblasts. Isolation of trophoblast subtypes is technically challenging. Upon removal, syncytiotrophoblasts disintegrate and invasive cytotrophoblasts are admixed with uterine cells. We used laser capture to circumvent these obstacles. This enabled isolation of syncytiotrophoblasts and two subpopulations of invasive cytotrophoblasts from cell columns and the endovascular compartment of spiral arteries. Transcriptional profiling revealed numerous genes, the placental or trophoblast expression of which was not known, including neurotensin and C4ORF36. Using mass spectrometry, discovery of differentially expressed mRNAs was extended to the protein level. We also found that invasive cytotrophoblasts expressed cannabinoid receptor 1. Unexpectedly, screening agonists and antagonists showed that signals from this receptor promote invasion. Together, these results revealed previously unseen gene expression patterns that translate to the protein level. Our data also suggested that endogenous and exogenous cannabinoids can affect human placental development.
Highlights
At birth, the human placenta is the newborn’s largest organ (Pryce et al, 2014)compared to those of the body, its weight is approximately double that of the heaviest, the brain (Boyd and Hamilton, 1967)
At an electron microscopic level, the syncytiotrophoblasts that form the outer surface of the villi are covered with branched microvilli, which substantially add to the surface area, by our estimate producing at least a 10-fold increase (Wislocki and Dempsey, 1955)
The focus was on areas that by macroscopic inspection included spiral arteries with dilated termini, a sign of CTB invasion
Summary
The human placenta is the newborn’s largest organ (Pryce et al, 2014)compared to those of the body, its weight is approximately double that of the heaviest, the brain (Boyd and Hamilton, 1967). During the last six months of pregnancy, placental weight increases over seven-fold (Boyd and Hamilton, 1967) while simultaneously supporting over a thirty-fold increase in that of the fetus (Armitage et al, 1967). At term the total area in direct contact with maternal blood is estimated to be ~12 m2 (Boyd, 1984). At an electron microscopic level, the syncytiotrophoblasts that form the outer surface of the villi are covered with branched microvilli, which substantially add to the surface area, by our estimate producing at least a 10-fold increase (Wislocki and Dempsey, 1955). The human placenta is hemochorial, i.e., in direct contact with uterine blood, minimizing the cellular barriers between the maternal source of nutrients and oxygen, and the placental vasculature that carries these substances to the embryo/fetus
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