Chapter 1 – The placental bed in a historical perspective



Chapter 1 The placental bed in a historical perspective



Robert Pijnenborg

Katholieke Universiteit Leuven, Department Woman & Child, University Hospital Leuven, Leuven, Belgium



The discovery of the placental bed vasculature


Placental vasculature, in particular the relationship between maternal and fetal blood circulations, has been a contentious issue for a long time. It was indeed a matter of dispute whether or not the fetal blood circulation was separate from or continuous with the circulation of the mother as stated by the Roman physician Galen (129–200). The Renaissance anatomist Julius Caesar Arantius (1530–1589) is usually quoted for being the first who explicitly denied the existence of any vascular connection between the mother and the fetus in utero [1,2]. Although this opinion was seemingly based on careful dissections of human placentas in situ, he obviously did not have the tools to trace small blood vessels in sufficient detail to provide full support for this idea. Moreover, before William Harvey (1578–1657) anatomists did not understand the relationship between arteries and veins, and thus their knowledge about the uteroplacental blood flow in the placenta must have been rather confused.


The brothers William (1718–1783) and John Hunter (1728–1793) are credited for having demonstrated the separation of maternal and fetal circulations by using colored wax injections of human placentas in utero. It was probably the younger brother John who did all the work, and he claimed afterwards most of the credit for this finding [3]. In his magnificent Anatomy of the human gravid uterus (1774) William Hunter included the first drawing of spiral arteries (‘convoluted arteries’), in what must have been the very first illustration of a human placental bed (Fig. 1.1) [4]. These ‘convoluted arteries’ are embedded in the decidualized uterine mucosa, the term ‘decidua’ being used for the first time by William Hunter to describe the ‘membrane’ enveloping the conceptus, which is discarded at parturition (Latin decidere, to fall off). This obviously referred to the decidua capsularis, typical for humans and anthropoid apes, which is formed as a result of the deep interstitial implantation of the blastocyst in these species. John Hunter, however, pointed out that there is also a ‘decidua basalis’ underneath the placenta. In a tubal pregnancy case he noticed that a similar tissue had developed within the uterus, and he therefore concluded that the decidua originates from the uterine mucosa [5].





Fig. 1.1 View of the placental bed after removal of the placenta, showing stretches of spiral arteries. Illustration from William Hunter’s Anatomy of the human gravid uterus (1774).



Early ideas about placental function


Hunter’s demonstration of separate vascular systems coincided with Lavoisier’s discovery of oxygen and its role in respiration. It was found that the uptake of oxygen by the blood is associated with a shift in color from a dark to a light red. This color-shift was observed in lungs as well as in the gills of fish, and it was Erasmus Darwin (1731–1802), grandfather of Charles Darwin, who pointed out that exactly the same happens in the placenta [6]. Furthermore, Erasmus Darwin tried to understand how the oxygenated maternal blood is delivered to the fetus. He had noticed that after separation of the placenta, uterine blood vessels start bleeding, while the placental vessels do not. For him this was an indication that the terminations of the placental vessels must be inserted into the uterine vasculature while remaining closed off from the maternal circulation. He thought that structures, referred to as ‘lacunae of the placentae’ by John Hunter, might represent ‘cells’ filled with maternal blood from the uterine arteries. It is obvious that these ‘cells’ referred to compartments of the intervillous space. Erasmus Darwin went as far as to equate these ‘lacunae of the placentae’ to the ‘air-cells’ (alveoli) of the lungs. Also interesting is the comparison he made with cotyledonary placentas of cows, which after separation do not result in bleeding of uterine blood vessels. Of course he was unaware of structural differences between the human hemochorial and the cow’s epitheliochorial placenta. His speculation on a ‘greater power of contractions’ of uterine arteries in cows almost suggests an intuitive grasp about differences in uteroplacental blood supply between humans and cows [7], foreshadowing the later concept of ‘physiologically changed’ spiral arteries in the human [8].


While the ideas of eighteenth century investigators about the respiratory function of the placenta were essentially correct, opinions about a possible nutritive function of the placenta were very confused. The Scottish anatomist Alexander Monro (1697–1767) thought that, analogous to nutrient uptake in the intestines, a ‘succulent’ substance appeared between the uterine muscle and the placenta (i.e. the decidual region), which he thought would be absorbed by ‘lacteal vessels’ of the placenta [2]. In his opinion these placental vessels had to be open-tipped and had to cross the placental–uterine border for absorbing the uterine nutritious material. This idea was of course refuted by Hunter’s injection experiments, which clearly showed that fetal vessels never end up in the uterine wall. Transmembrane transport mechanisms for glucose, lipid and amino acid transfer were obviously unknown at that time, and investigators like Erasmus Darwin therefore tended to minimize the idea of a possible nutritive function of the placenta. Instead he favored the view that the amniotic fluid was the main source of fetal nutrition, an idea that he had borrowed from William Harvey, but which became overruled by later findings.



The discovery of trophoblast invasion


A major technological advance in the nineteenth century was the perfection of the microscope together with the development of histological techniques for tissue sectioning and staining. The first microscopic images of the human placenta were obtained in 1832 by Ernst Heinrich Weber, revealing the organization of fetal blood vessels within villi, which are lined by a ‘membrane’ separating the fetal from the maternal blood. For several decades there was uncertainty about the nature of this outer villous ‘membrane’, and it was originally thought that this layer represented the maternal lining (endothelium) of the extremely dilated uterine vasculature [9]. The origin of this tissue layer and the real nature of the intervillous space could only be clarified by histological investigations from early implantation stages onwards. An early pioneer was the Dutch embryologist Ambrosius Hubrecht (1853–1915), who undertook the study of implantation in what he considered to be representative species of primitive mammals, hedgehogs and shrews. The idea behind this work was that the implantation events in primitive mammals might offer clues about the evolution of viviparity. His famous hedgehog study revealed early appearance of maternal blood lacunae engulfed by the outer layer of extraembryonic cells. He considered the latter as feeding cells and hence introduced the term ‘trophoblast’ [10].


Slowly investigators began to realize the invasive potential of this trophoblast. The French anatomist Mathias Duval (1844–1907) was probably the first to recognize the invasion of trophoblast (placenta-derived ‘endovascular plasmodium’ in his terminology) into endometrial arteries, in this case in the rat [11]. He published his findings in 1892, but he was not the first to have seen endovascular cells in maternal vessels. Twenty years before, in 1870, Carl Friedländer had reported the presence of endovascular cells in ‘uterine sinuses’ of a human uterus of 8 months’ pregnancy [12]. He notified the rare occurrence of arteries in this specimen, obviously not realizing that these might have been transformed by endovascular cell invasion. He was unable to decide whether these cells were derived from the placenta or the surrounding maternal tissue, but he reported their presence as deep as the inner myometrium. His illustrations show two vessels of his 8 months specimen, one completely plugged, the other containing only a few intraluminal cells (Fig. 1.2). In the latter he noted the presence of a thickened homogeneous ‘membrane’ containing dispersed cells in the vessel wall (Fig. 1.2, parts 1b and 2c, recognizable as the fibrinoid layer with embedded trophoblast), and also an organized thrombus with young connective tissue (Fig 1.2, part 2e, recognizable as a thickened intima overlying the fibrinoid layer). He also obtained a postpartum uterus in which he thought he could recognize similar ‘sinuses’ (Fig 1.2, part 3). Surprisingly, Friedländer thought that most intravascular cells were multinuclear (Fig 1.2, part 4). He reasoned that the presence of endovascular cells must considerably slow down and even interrupt the maternal blood supply to the placenta, and considered that failed vascular plugging might result in intrauterine bleeding and maternal death. Friedländer’s contemporaries favored the idea that the intravascular cells must have been sloughed off from the maternal vascular wall. It wasn’t until the early twentieth century that investigators such as Otto Grosser [13] began to consider these cells as trophoblastic.


Sep 22, 2020 | Posted by in GYNECOLOGY | Comments Off on Chapter 1 – The placental bed in a historical perspective
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