Boyd Slides
These are a selection of placenta-in-situ slides from various stages of gestation, obtained from pregnant hysterectomies performed in the 1950-1960s. They are available as low-resolution scans on the CTR website.
Note that in most cases the placenta is unusually low-lying. This may have caused bleeding and precipitated the hysterectomy.
Features to identify are:
- The regression of villi in the early specimens to form the smooth membranes (chorion laeve). Note that the regressing villi are avascular, hypocellular, have a thin trophoblast and are associated with maternal erythrocytes in the intervillous space. These are absent from the more central regions of the placenta. We speculate regression is due to locally high levels of oxidative stress following onset of the maternal circulation.
- The reduction in thickness of the endometrium as pregnancy advances. In the later specimens the basal plate appears almost apposed to the myometrium.
- The presence of multinucleated trophoblast giant cells in the myometrium, marking their point of furthest invasion.
- The general increase in density of the villous trees as gestation advances.
Licensing: CTR Boyd Collection by Centre for Trophoblast Research is licensed under CC BY-NC-SA 4.0   
Select the slides to view high resolution image:
| 1. | [H710]
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This is the earliest specimen in terms of gestational age, approximately 6.1 weeks, in the collection and so one of the most informative. The implantation site prior to dissection from the uterus is illustrated in Boyd and Hamilton's book 'The Human Placenta', and it can be seen as an elevated area protruding into the uterine lumen. Although human implantation is described as highly invasive, the conceptus actually only comes to lie in the superficial stratum compactum of the endometrium. There is now evidence that endometrial cells grow over the conceptus to encapsulate it and repair the uterine epithelium, forming the decidua capsularis. As the underlying endometrium undergoes involution as gestation advances, so the conceptus sinks deeper into the uterine wall. The migratory extravillous trophoblast cells are, of course, invasive and normally penetrate as afar as the inner third of the myometrium. One of the most conspicuous features of this specimen is the thickness of the decidua basalis, 5-6 mm, underneath the developing placenta. The endometrial glands are prominent and highly active, with a mixture of carbohydrates, glycoproteins and lipid droplets in their lumens. There are numerous examples of where the glands can be seen communicating with the intervillous space through openings through the basal plate. Sections stained with PAS reveal the accumulation of glycogen in the syncytiotrophoblast of villi close to these openings, particularly on the aspect of the villi facing the glands. This feature, along with recent immunostaining for glycodelin A, one of the principal gland products, confirms that the secretions are taken up by the placenta as a form of histotrophic nutrition. The gland secretions also contain a range of growth factors that stimulate trophoblast proliferation and differentiation. Examples of coiled maternal spiral arteries can also be seen within the decidua basalis. These are all of narrow calibre and have not yet undergone significant remodelling. Boyd and Hamilton noted that communication between the arteries and the intervillous space cannot be observed at this stage of gestation, and we now appreciate that early development takes place in a physiological, low-oxygen environment. This likely protects the embryo against free-radical mediated teratogenesis.
The superficial aspect of the chorionic sac has been opened in the middle to remove the embryo, but towards the periphery the sac remains complete. As can be seen, villi are formed over the entire surface of the sac, forming the chorion frondosum. The villi are mainly of the immature intermediate variety, characterised by the loose stromal core. Processes from the stromal cells unite to form fluid-filled channels, and fetal macrophages can often been seen within the channels. These have differentiated in situ. Vascularisation of the villi is limited, and any vessels contain nucleated erythrocytes. There is not an effective fetal circulation through the villi at this stage, and the stromal channels likely facilitate diffusion of nutrients and metabolites. The villi are covered by an outer layer of syncytiotrophoblast, beneath which is a complete layer of progenitor cytotrophoblast cells. Proliferation of the trophoblast is prolific at this stage of gestation, driven by the histotroph from the endometrial glands. Where anchoring villi make contact with the decidua they are continued as the cytotrophoblast cell columns. Cells at the proximal end of the column in contact with the trophoblast basement membrane represent a progenitor niche. Cell division here leads to formation of the column. As the cells progress along the column they lose their mitotic potential and undergo an epithelio-mesenchymal transition and differentiate into extravillous trophoblast. At their distal ends, cells from adjacent columns spread laterally and merge to form the cytotrophoblastic shell. This forms the interface with the endometrium/decidua, and can be clearly seen in this specimen. The cytotrophoblast cells of the shell contain large amounts of glycogen that have been eluted during the fixation process. The cytoplasm of the cells therefore appears empty and pale staining.
On the maternal aspect of the shell can be seen numerous examples of the invasive interstitial extravillous trophoblast cells. These differentiate from the shell, and in doing so acquire a spindle-like morphology and are darkly staining. These cells migrate around the spiral arteries where they interact with the maternal immune cells, especially the uterine Natural Killer cells. There interactions promote remodelling of spiral arteries through the release of cytokines. The interstitial trophoblast also break into the endometrial glands, facilitating the discharge of their secretions though the basal plate. The secretions can also be seen dissipating through the extracellular matrix of the endometrium at the materno-fetal interface. Data from in vitro experiments suggest that glycoproteins such as glycodelin A may influence trophoblast invasion and the local maternal immune response. The first strands of Nitabuch’s stria can be observed at the interface of the shell and the endometrium/decidua.
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| 2. | [H916a]
[H916b]
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This specimen is of approximately 8.5 weeks gestational age. It shows the placenta-in-situ in a complete uterus, with the cervix projecting inferiorly. A tiled-scan of another section that provides the ability to zoom in to some degree can be viewed elsewhere on the CTR website. The placenta is clearly very low lying in the uterus and covers the internal opening of the cervical canal, a placenta praevia. No clinical details are available, but the patient may have presented with severe bleeding. The three areas of the decidua can easily be appreciated in this section, the decidua capsularis covering the superficial aspect of the chorionic sac, the decidua parietalis of the opposite uterine wall, and the decidua basalis underlying the placenta. Active endometrial glands can be seen in the decidua parietalis and basalis, although the basalis is much thinner than in H710, which is 2.5 weeks earlier. The decidua capsularis and parietalis have not yet fused, and so a portion of the uterine lumen is still visible towards the top of the section. Fusion usually occurs at around 12-14 weeks of gestation. The villi over the superficial pole of the chorionic sac have already undergone considerable regression, and are much less extensive than those opposite the decidua basalis.
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| 3. | [H876] |
This specimen is of approximately 9.3 weeks gestational age. Although labelled as placenta, no placental tissue appears to be present in the section. Instead, it appears to be a section through the uterus, maybe peripheral to the placental disc. It does show well the three layers of the endometrium/decidua; the stratum compactum superficially into which the conceptus implants, the stratum spongiosum comprising the bodies of the endometrial glands, and the stratum basale that contains the bases of the glands and from which the endometrium regenerates during the normal menstrual cycle.
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| 4. | [H643] |
This specimen is of approximately 10 weeks gestational age. The section shows only the decidua basalis under the developing placenta and a portion of villi, and there is no myometrium or chorionic plate. Hence, orientation is difficult. The decidua basalis is irregular in thickness, and contains numerous active endometrial glands. Secretions can be seen within their lumens, and in the sections stained with trichrome these can be seen to be a mix of lipid droplets (staining red) and carbohydrate/proteinaceous material (staining blue). Examples of spiral arteries undergoing remodelling can also be observed, as confirmed by the surrounding fibrinoid material. The accompanying dilation is quite marked, and serves to reduce the velocity and pressure with which the maternal blood enters the intervillous space. The villi are mostly of the immature intermediate and mesenchymal types. The former are characterised by their loose mesenchymal stromal core. The stromal cells form a series of fluid filled channels at this stage of gestation, which should not be misinterpreted as an oedematous change. The channels may assist with the diffusion of oxygen and nutrients as an effective fetal circulation through the villi has yet to be established. Fetal macrophages (Hofbauer cells) are frequently seen within the channels, and may play a role in immune surveillance. The macrophages are large round cells, and their cytoplasm has a grey appearance because of extensive vacuolation. The villi have an outer covering of syncytiotrophoblast, and by this stage the underlying layer of progenitor cytotrophoblast cells is incomplete.
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| 5. | [H630a]
[H630b]
[H630c]
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This specimen has a gestational age of approximately 9.8 weeks, and provides a good overview of the implantation site and the developing membranes. The section covers the main part of the placenta and also its margin on the right-hand side. Beyond the margin can be seen some of the decidua parietalis, that is the decidualised endometrium of that part of the uterus not involved with the implantation. The decidua parietalis undergoes the same hormonal changes as the decidua basalis beneath the developing placenta, but there is no trophoblast invasion. Hence, you can see active, dilated endometrial glands and unremodelled, narrow calibre spiral arteries. The decidua basalis under the developing placenta is still several millimetres thick, although the thickness is highly variable across the placental bed. Active glands containing secretions can still be observed, and remodelled spiral arteries can be identified by the clustering of their cross-sectional profiles and the dense accumulation of fibrinoid material surrounding them. Deeper in the myometrium can be seen branches of the arcuate and radial arteries that feed the spiral arteries. The developing basal plate interfacing between the placenta and decidua basalis is very irregular, following the contour of the decidua. Nitabuch’s stria is a prominent feature, separating the extravillous trophoblast cells of the anchoring villi and the maternal decidual cells. Fibres of the stria blend with the extracellular matrix surrounding the extravillous trophoblast, and also that of the decidua. Hence, it helps to anchor the developing placenta. Villi are relatively poorly developed at this stage. They contain few blood vessels, and these are often located deep within the stromal core and are not yet optimised for diffusional exchange. The villi covering the superficial pole of the chorionic sac have undergone considerable regression by this stage, but the intervillous space surrounding them is still continuous with that of the future definitive placenta on the right-hand side. Eventually, the superficial villi totally regress and the space will be occluded, resulting in the formation of the smooth membranes. The regressing villi are referred to as the chorion laeve.
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| 6. | [H789a]
[H789b]
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This specimen is of approximately 10.4 weeks gestational age, and comprises a placenta still within the entire uterus. The uterus had been incised but the two halves have been pushed together to recreate the whole. It therefore provides an excellent example of the relationship of the conceptus to the uterine cavity at this stage of gestation. As can be seen, the chorionic sac protrudes out into the uterine lumen. It is covered by the decidua capsularis which overgrows and encapsulates the conceptus following implantation. The decidua capsularis has not yet fused with the decidua parietalis of the opposite uterine wall, and so the uterine lumen is still patent. The villi that initially grew over the superficial pole of the chorionic sac have undergone almost complete regression in the central region to form the chorion laeve or smooth membranes. A gradation in regression exists and some villi persist on the lateral aspects of the sac, blending with those of the developing definitive placental disc in contact with the decidua basalis. The basal plate is uneven at this stage of gestation. Spiral arteries undergoing remodelling can be observed within the decidua basalis.
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| 7. | [H1094]
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This specimen is of approximately 14 weeks gestational age. A tiled-scan of an H&E stained section that provides the ability to zoom in to some degree can be viewed elsewhere on the CTR website. The specimen shows the placenta in the entire uterus. The placenta is very low lying, and covers the internal opening of the cervical canal; a placenta praevia. This is very atypical, and may be the reason behind the hysterectomy. The section provides an appreciation of the relationship of the placenta and chorionic sac to the uterus. The villi over the superficial pole of the sac have regressed to form the membranes, and these are applied to the decidua parietalis of the opposite uterine wall. The apposition has not extended top the fundic region of the uterus where the uterine lumen persists and the decidua capsularis can still be identified. The decidua basalis is irregular in thickness. Several spiral arteries undergoing remodelling are present, and there is endovascular trophoblast plugging still in at least one case.
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| 8. | [H911] |
This specimen is an isolated placenta of approximately 15.6 weeks gestational age. It shows the complete chorionic sac, with the developing definitive placenta blending with the regressing villi of the chorion laeve. A notable feature is the infolding of the basal plate to form placental septa that extend towards, but do not reach, the chorionic plate. The septa subdivide the placenta into a series of lobes and may assist in directing the maternal blood flow. Because of their origin, septa may contain endometrial glands and maternal decidual cells. This needs to be borne in mind when performing genomic analyses. Maternal arterial openings through the basal plate are often associated with the base of a septum.
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| 9. | [H1028a]
[H1028b]
[H1028c]
[H1028d]
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This specimen is of approximately 17 weeks gestational age. The placenta is now taking on its more mature form. The section covers the central part of the placental disc but also the marginal zone and the transition to the membranes. There has been some separation of the placental margin from the uterine wall during processing, but elsewhere the apposition of the basal plate to the uterus is intact. The basal plate is still somewhat irregular and undulating. The decidua basalis is very thin, and in areas the basal plate is closely approximated to the myometrium with only a scattering of decidual cells, a few remnants of endometrial glands, and a plexus of thin-walled vessels intervening. Infoldings of the basal plate can be seen forming septa that partially divide the intervillous space. Larger profiles of endometrial glands and clusters of decidual cells can be seen within the bases of the septa, confirming the mechanism of their formation. Nitabuch’s stria marking the interface between the fetal and maternal tissues is a prominent feature staining pink. Remodelled spiral arteries characterised by the thick mantle of surrounding fibrinoid material can be seen approaching and, on occasions, entering through the basal plate. Venous openings can also be identified, and distinguished because they connect with the plexus of thin-walled vessels immediately beneath the basal plate. Villi often protrude through the venous openings, whereas the arterial openings are unobstructed and communicate with a relatively villous-free area of the intervillous space. These contrasting appearances no doubt reflect the different haemodynamics of the two sets of openings. On the opposite face of the placenta the chorionic plate is well-formed, and stem villi can be seen projecting from the undersurface. The amnion is applied to the fetal surface, but it can still be stripped away at term after delivery.
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| 10. | [H728] |
This specimen is of approximately 18 weeks gestational age. The section goes across the placental disc and the smooth membranes can be seen extending from the margins of the disc on either side. On the right the membranes are applied to the decidua parietalis whereas on the left they are still in the form of the decidua capsularis. On the left, the decidua parietalis can be seen to be continuous with a thin layer of decidua capsularis that would have extended over the placenta disc, enclosing the amniotic cavity. Regressing villi of the chorion laeve surrounded by maternal blood can be observed sandwiched between the amnion and the decidua capsularis. The myometrium is folded, which may reflect shrinkage during processing, and contains good examples of the arcuate and radial arteries. The decidua basalis is generally thin, although variable in thickness across the placental bed. In some areas profiles of endometrial glands still containing secretions in their lumens can be observed. In other areas the basal plate seems to be almost apposed to the myometrium with only a vascular plexus separating the two. Nitabuch’s stria, the layer of fibrinoid material in the basal plate that separates fetal extravillous trophoblast cells from the maternal decidual cells can be seen staining red.
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| 11. | [H735] |
This specimen is of approximately 21.5 weeks gestational age. Some sections cover the developing placenta and surrounding uterine wall, but the arrangement has been distorted presumably through contraction of the myometrium. Hence, the placenta appears rather globular. The maternal vasculature was injected with ink during processing, and this has accumulated in the relatively villous-free subchorionic lake just below the chorionic plate. Of note is the way the smooth membrane extends from the margin of the placental disc over the surface of the decidua parietalis on the right of the section. Note also how the decidua basalis and parietalis are continuous, although the former is very much thinner than the latter.
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| 12. | [H724] |
This specimen is of approximately 23 weeks gestational age. This large section encompasses the complete placental disc and the smooth membranes that extend on either side applied to the decidua parietalis. The section shows nicely how the chorionic and basal plates come together at the margin of the disc to seal the intervillous space, and how the membranes are continuous with the fused chorionic and basal plates. Unfortunately, during fixation the basal plate has separated from the decidua basalis over large areas due to differential shrinkage of the tissues involved.
Nonetheless, it can be appreciated by thin the decidua basalis is at this stage of gestation. A few remnants of endometrial glands and decidua cells are present, most prominently in the regions where the basal plate is infolded to form a placental septum. Otherwise, it appears that the basal plate is closely approximated to the myometrium, separated only by the extensive vascular plexus. These thin walled vessels provide an easy plane of cleavage at the time of delivery, as is mimicked here by the artefactual shrinkage. The villus trees are becoming much more dense at this stage than previously, and there are many more small villous profile reflecting the proliferation of terminal villi. Villi are relatively few under the chorionic plate, where the large intervillous spaces comprise the sub-chorionic lake. This may assist in venous drainage of the intervillous space, but the relatively slow rate of maternal blood flow means that fibrin is often deposited in this region. Such depositions are of little physiological significance unless they become excessive and compromise maternal blood flow or villous exchange surface area. The amnion can be seen loosely adherent to the fetal side of the chorionic plate.
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| 13. | [H725] |
This is an isolated placenta of approximately 24.5 weeks gestational age. The section shows the placenta and the smooth membranes as a complete sac. Both the basal and chorionic plates are well displayed. The villus trees are uniformly dense, reflecting the rapid formation of terminal villi during the second half of gestation. There is no evidence of a sub-chorionic lake in this specimen, as there is in H724. The amnion is closely adherent to the fetal side of the chorionic plate, and the umbilical cord with its two arteries and single vein can be seen blending with the central part of the plate.
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| 14. | [H1053a]
[H1053b]
[H1053c]
[H1053d]
[H1053e] |
This specimen if of approximately 27 weeks gestational age. The section covers the whole placenta, and is about 11 cm in width. A tiled-scan that provides the ability to zoom in to some degree can be viewed elsewhere on the CTR website. Here, some orientating images are provided. In addition, some smaller sections taken from the margin of the placenta have been whole-slide scanned. Unfortunately, where the section was taken the basal plate had separated from the myometrium during processing, but nonetheless the villi are well preserved. The placenta has by now taken on the definitive form, with clearly defined chorionic and basal plates and the membranes extending from the margin of the disc. The umbilical cord can be seen inserting on the chorionic plate in some sections, with branches of the vessels radiating outwards within the substance of the plate. The amnion is applied over the fetal surface of the chorionic plate, and stem arise from its undersurface. The villi are much denser than earlier in gestational due to the elaboration of terminal villi, and consequently the dimensions of the intervillous clefts between adjacent villi are smaller. This change in porosity will impact on the rate of maternal blood flow through the placenta, which slows as gestation advances. Most villous profiles are of the mature intermediate and terminal types.
The endometrium beneath the basal plate is very thin, and in areas the plate is separated from the myometrium only be a plexus of thin-walled vessels. The few decidual cells present are enmeshed in the fibrinoid material of the basal plate and will be shed as part of the placenta at delivery. The membranes extend from the margin of the disc where the chorionic and basal plates merge. They are applied to the surface of remnants of the decidua parietalis.
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| 15. | [Term placenta resin 40 weeks] |
This specimen has been fixed by perfusion at physiological pressure and illustrates the fetal capillaries in their distended state. The fetal capillaries within terminal villi show local dilatations called sinusoids. This dilation brings the capillary endothelium in close contact with the overlying syncytiotrophoblast, which is locally thinned. At these points the distance between the fetal and maternal circulations is reduced to 2-3 µm, and computational modelling has shown them to be the principal sites of diffusional exchange. The arteries within the stem villi represent the resistance vessels of the fetal placental circulation, and are important for regulating regional flow in the placenta and for matching maternal and fetal perfusion. Because of the lack of nerves within the placenta, vasomotor control is under the influence of local agents, including nitric oxide and hydrogen sulphide. The stem villi are the supporting framework of the placenta, and have a dense stromal core. They are poorly vascularised with capillaries and so play little direct role on placental exchange. Terminal villi are characterised by the presence of large dilated fetal capillaries and the formation of vasculosyncytial membranes. The volume and surface area of terminal villi expand exponentially from approximately 20 weeks' gestation, increasing the functional capacity of the placenta. As their name suggests, intermediate villi lie between stem villi and terminal villi in the branching pattern of the villous tree. They contain more fetal vessels than stem villi, but generally do not display vasculosyncytial membranes. They are therefore involved to a greater extent than stem villi in maternal-fetal exchange. Terminal villi arise from the lateral aspects of intermediate villi, and there is no clear boundary between the two. The structure at the lower tip of this profile bears many of the characteristics of a terminal villus, with dilated capillaries and an extensive vasculosyncytial membrane. The outer layer of trophoblast is formed by a continuous multinucleated layer of syncytiotrophoblast that is involved in hormone synthesis and active transport between the maternal and fetal circulations. Cytotrophoblast cells are still present at term and represent a progenitor population that feeds into and expands the syncytiotrophoblast. Fusion is regulated by the expression of retroviral envelope proteins, the syncytins. This villus displays many cytotrophoblast cells. These lie on a trophoblastic basement membrane that separates the trophoblast from the stromal core. The total number of cytotrophoblast cells continues to increase until term, but they are less commonly seen in any single villus profile as the latter expand at a greater rate. They can be identified from their position and characteristic paler staining.
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| 16. | [Term human placenta] |
The chorionic plate forms the boundary of the placenta facing the fetus, and to which the umbilical cord is attached. It is rich in collagen fibres (staining blue). Early in pregnancy the surface facing the intervillous space is lined by syncytiotrophoblast, but towards term this degenerates and is replaced by fibrinoid material (Langhans' fibrinoid). Stem villi arise from the chorionic plate. Stem villi are characterised by the dense stromal core, the presence of muscular arterioles and the absence of any capillaries for exchange. Intermediate villi arise from such branches and give rise in turn to terminal villi. Stem villi provide the supporting framework for the peripheral villous trees. They contain large arteries and veins that connect with the chorionic vessels radiating from the umbilical cord. The walls of their arteries are rich in smooth muscle, and these represent resistance vessels that will aid distribution of the fetal circulation to different areas of the placenta. In the absence of autonomic nerve fibres in the placenta, vasomotor tone is dependent of local gasotransmitters, including nitric oxide, carbon monoxide and hydrogen sulphide. Terminal villi are the final branches of the villous tree and are the functional region of the placenta in terms of exchange. They do not contain arteriols, but have a high density of dilated capillaries. These come close to the villous surface, so facilitating gaseous and other diffusional exchange. Intervillous space is a relatively villus-free area and may represent the central cavity of a placental lobule. If so, maternal blood is delivered into this region from the spiral artery and then disperses between the denser peripheral villi. Fibrin deposition - the fibrin is of little significance unless it becomes excessive and compromises maternal blood flow and the surface area for exchange.
The equivalent of Langhan's fibrinoid under the chorionic plate, Rohr's stria is composed of fibrin-type fibrinoid. It reflects areas of sluggish maternal blood flow and may enmesh anchoring villi. Maternal decidual cells have been incorporated into a placental septum through infolding of the basal plate. A few layers of extravillous trophoblast contribute to the formation of the basal plate. They are remnants of the cytotrophoblastic shell and arise from the cell columns of anchoring villi. They are separated from the decidual cells by the fibres of Nitabuch's stria. This layer forms at the maternal-fetal interface and is here staining red.
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| 17. | [Umbilical cord] |
There is only one umbilical vein in the human, in contrast to some species. The vein can be identified by the smaller amount of smooth muscle in the vessel wall. The umbilical arteries contain a lot of smooth muscle in their walls, which contracts when the cord is exposed at delivery restricting further blood flow to the placenta. The two umbilical arteries are linked by an anastomosis (Hyrtl's anastomsis) close to the attachment of the cord to the chorionic plate. This is thought to aid distribution of the umbilical blood flow. The umbilical cord originates as the connecting stalk of the embryo, and becomes ensheathed with amnion as the latter expands and fills the coelomic cavity. Allantoic duct is all that remains of the allantois in the human. It is an extension of the fetal bladder into the umbilical cord, the two being connected by the urachus. The allantois is a large sac in other species and fills with urine and waste products as pregnancy advances. It is thought that the human placenta is more permeable to these products and so there is not the same need to store them in the gestational sac. Nonetheless, the arteries associated with the allantois still vascularise the human placenta, and hence it is of the chorio-allantoic type. These are the umbilical arteries, and because of its origin they run alongside the bladder up to the umbilicus.
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