Book - Contributions to Embryology Carnegie Institution No.1-3
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Mall FP. On the fate of the human embryo in tubal pregnancy. (1915) Contrib. Embryol., Carnegie Inst. Wash. Publ. 221, 1: 1-104.
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Normal Embryos in the Uterus
It is now generally admitted that in normal implantation the ovum penetrates the uterine wall and attaches itself within the mucosa. This fact, which was first established by Count Spee, was subsequently confirmed by Peters and other competent investigators. Fairly conclusive evidence was adduced by Brj^ce and Teacher in the careful study of their well-known specimen. When the ovum first reaches the uterus it rapidly penetrates the mucous membrane and forms a cavity for itself by secreting a substance which destroys the cells, the ovum being encircled by a layer of dead cells. It may be proper at this point to state that this process of destruction is observed wherever the ovum comes in contact with maternal tissue. The cells undergo a curious hyaline transformation and are converted into a fibrinoid mass often spoken of as fibrin ; but this mass is compact and not intermingled with individual cells. It is sometimes spoken of as canalized fibrin. The word "fibrin" in this connection is a misnomer, as was pointed out by Professor Grosser, who constantly speaks of this substance as "fibrinoid." If we add to this the word "necrosis," it seems to me that the term, fibrinoid necrosis would describe the condition as well as our present knowledge warrants.
The entrance of the ovum into the mucous membrane is accomplished, as a rule, by a profuse local hemorrhage into the cavity which the ovum has burrowed out for itself. This is shown especially well in the specimen by Bryce and Teacher (their Plate III) and in a somewhat older specimen by Peters. As all of these observations were made upon specimens with a questionable history, it is not clearly determined whether the hemorrhage is to be viewed as a normal or as a pathological process. However, it seems to me that this question has been fully set at rest by Herzog, who obtained an ovum with normal implantation from a woman who had died from a puncture wound of the heart. We have here a specimen undoubtedly normal in which the hemorrhage is practically identical with that in Peters's specimen. Below the point of implantation there are large sinuses of maternal blood into which the trophoblast extends, and in turn the blood reaches to the chorionic membrane, filling entirely the small spaces between the villi, which are just beginning. We have here a true intervillous hemorrhage which many often speak of as a primitive intervillous circulation. On the other hand, we have two other young human ova in which there is practically no blood in the intervillous spaces. The one recorded by Jung is from uterine scrapings. The specimen is somewhat older than that of Peters. It was removed with a large mass of uterine mucous membrane attached, so if the intervillous spaces had been normally filled with blood, it is not improbable that it would have run, leaving the empty spaces filled with clear fluid.
The other case is that of Strahl and Beneke, whose specimen was also obtained from uterine scrapings. In this case a number of large vessels and sinuses in the neighborhood of the ovum are filled with blood, but most of the intervillous spaces are empty.
A similar specimen found in situ by Frassi establishes the theory that the freshly implanted ovum is not always embedded in a mass of blood. In the Frassi specimen the intervillous spaces were found empty, but in direct contact with the uterine veins. Frassi, however, concludes that this condition does not speak against an intervillous circulation, but rather in its favor; and this opinion is also entertained by Grosser.
In our own collection we have a specimen about the size of Herzog's or Peters's with practically the same intervillous hemorrhage. The specimen (No. 763) is somewhat more advanced than either of the two others; it was obtained from uterine scrapings and appears to be normal in every respect. However, in later stages it does not appear as though the hemorrhage is as pronounced as in some of the earlier specimens studied. In fact, this point has been commented upon frequently, and it is usually stated that the absence of blood between the villi is due to contraction of the uterus when the entire organ is removed at operation or to ruptured intervillous spaces when the specimen is obtained from the abortion. It has always seemed to me probable that in the latter instance the rupture has allowed the blood to enter instead of escape and that in the former it is very remarkable that the contraction of the uterus should have pressed out the blood corpuscles and allowed the blood plasma to remain. At any rate, in older specimens which have been examined in situ it is difficult to show that an intervillous circulation exists. Some embryologists have overcome this possibility by stating that intervillous circulation is a condition peculiar to the second half of pregnancy. After examining several well-preserved specimens in situ, I am convinced that this question is by no means settled, and must still be regarded as open.
At this point the findings of two excellent specimens may be cited. One is from an ovum and uterus containing a normal embryo 26 mm. long (No. 782) and the other is from a specimen containing an embryo 4 mm. long (No. 836).
In the first specimen the entire uterus was hardened in strong formalin and was carefully cut into slabs, so that the attachment of the chorion to the uterus could be studied to advantage. There was practically no blood between the villi in this specimen and the tips of the villi were firmly attached to the uterine wall.
Between the villi were islands of necrotic trophoblast about 1 mm. in diameter and of a yellowish color. This seems to be the normal process in the development of the chorion, because as it advances there must be an extensive destruction of many of the primary branches of the villi. The condition may be compared to that observed in a dense forest of large trees, in which one can observe all stages of destruction of the branches that can not get sunlight. First, the branches near the main trunk of the tree die and then the larger branches succumb in case their tips do not reach the sunlight. Between the villi in this specimen there were found occasional hemorrhages and some amount of scattered blood. Whenever this blood comes in contact with the trophoblast, it in turn becomes active, for it has something to feed on, but in general the spaces between the villi are empty or partly filled with its degenerating branches, so there seems to be here no question regarding the absence of a normal intervillous circulation; without question, however, an extensive hemorrhage is often present in very early stages and specimens intermediate to those and the one just described are necessary in order to explain the transition from such specimens to those of Bryce and Teacher, Peters and Herzog, and No. 782, just described.
This stage we have in No. 836. The specimen came to the laboratory immediately after the operation, was carefully opened, and fixed alive in corrosive acetic. The specimen came from a young woman who had been married for 4 years, this being her first pregnancy. The uterus was removed for a myomatous condition. There was no history indicating any other disease. It was sent to the laboratory immediately and we succeeded in opening the uterus without injuring the implantation of the mass. The ovum was covered with decidua reflexa, below which tortuous vessels were apparent. On one side the sac (the implanted chorion) was adherent to the uterine mucosa (decidua vera). With a sharp scalpel the entire mass was dissected away from the uterus and brought under a binocular microscope in warm salt solution. The middle portion of the free surface was opened carefully, beautiful young villi being found, and the delicate wall of the chorion was next opened. Within were seen a transparent young embryo, 4 mm. long, and its umbilical vesicle. Through this opening in the chorion warm 40 per cent saturated aqueous solution of HgCl 2 containing 5 per cent glacial acetic acid was gently introduced and the entire mass placed in 500 c. c. of this fixation fluid. The main body of the uterus was dissected free from the myomatous nodule and fixed in 10 per cent formalin, the site of the implanted ovum being marked with a short wooden rod.
Later on the implanted chorion was cut into slabs and numerous photographs and drawings were made. This gave an opportunity to study carefully the villi and the spaces between them. The block which formed the middle zone of the ovum was about 4 mm. thick. The chorion was composed mostly of sharp white villi, with a small amount of blood at one point near the chorionic membrane; otherwise the intervillous spaces were filled with necrotic tips of villi or with a clear fluid. At the bases of the villi that is, on the uterine side the chorion was partly encircled with a hemorrhage which apparently involved the tips of the villi for about one-half of the base. Otherwise the tips had come into contact with the uterus without producing any hemorrhage. It appears, then, that in the earlier stages there is an extensive hemorrhage, so that there is sufficient blood to fill all the spaces between the villi, but later, as the ovum grows larger, the tips of the villi seem to protect the intervillous spaces by throwing up a wall or dam of trophoblast, which seems to hold back or plug the blood-vessels as soon as they have been eroded. The process is severe and must of necessity be accompanied with hemorrhages, but if these are not too extensive the effused blood can easily be devoured by the adjacent trophoblast. In general, however, this process is marked at the tips of the villi, but not between them. In fact, if there is a large hemorrhage, the ovum is rapidly detached, as is so frequently met with in tubal pregnancy. Sometimes in normal tubal pregnancies there are hemorrhagic areas measuring several millimeters in diameter. These seem to retard the growth of the ovum. If they are small, it appears as though the blood is prevented from forming a coagulum, possibly owing to some inhibitory substance secreted by the trophoblast. When the hemorrhage is large it appears as though this substance can not prevent coagulation, but in the neighborhood of the villi we usually have fluid blood, judging by the morphological appearances under the microscope.
Normal Embryos in the Tube
Among the many small ova found in the tube very few contain normal embryos. Either the embryo is deformed (as in No. 729), it is missing (as in No. 754), or the entire ovum is reduced to a small clot (as in Nos. 367 and 539). In these specimens the embryonic mass was either partly implanted or lying free in the tube lumen, showing that in many cases the ovum becomes detached, begins to disintegrate, and if not aborted into the abdominal cavity would ultimately be absorbed. In all probability abortion into the abdominal cavity is a common process, for we frequently see the ovum breaking up into pieces and scattered for long distances in the tube, and in some instances we have remaining a very few fibrous villi in the tube folds as the only indication of a pregnancy (plate 2, fig. 2).
If the pregnancy takes place in the uterine end of the tube, the ovum seems to find a better lodgment that is, it becomes implanted in the muscle wall and frequently eats through it. This is usually the case in an early perforation, for instance, in No. 729 (plate 10, fig. 3) the implantation was near the uterus, possibly at the attachment of the broad ligament. This burrowing into the tube wall could readily cause a perforation. If, however, attachment takes place on the broad-ligament side of the tube, perforation is less likely to occur immediately, but when it does occur it is into the broad ligament. This is easily understood, because it is only in this direction that the chorion can find sufficient tissue for a firm attachment. Such is the case in specimen No. 790, which contains an embryo 20 mm. long. Here there was such an extensive mixing up of the tissue that the specimen was at first believed to be one of ovarian pregnancy; more careful study, however, showed that it was a tubal pregnancy which had ruptured into the broad ligament.
We have in our collection one exceptionally good specimen of a tubal pregnancy containing a very small normal embryo. In this specimen, No. 808, the tube is uniformly distended for a distance of about 50 mm., having a diameter of about 15 mm. A good reconstruction of this specimen, after it had been cut into numerous sections, showed that the ovum was implanted on the broad ligament side near the uterine end for a distance of about 15 mm. and extended into the tube lumen towards the uterus for a distance of about 10 mm. and towards the abdominal end of the tube for about 40 mm. The tube lumen on the uterine end seems to be perfectly normal, and at the point of implantation it passes around the ovum on the side opposite the broad ligament. Opposite the middle of the attachment the outline of the tube is not very sharp, most of the tube wall having disappeared; its outer wall portion is only partially covered with epithelial cells. At this point the space between the ovum and the tube is distinguished by a layer of trophoblast covered by a large plug of necrotic tissue. This extends more or less around the circumference of the ovum until it reaches the point where the pregnancy mass has broken into the tube lumen. From here on the tube is lined with numerous wellformed folds which are more or less separated, probably owing to the distention. Beyond the pregnancy mass, within the inner opening of the tube, the lumen is filled with large, well-formed folds of mucous membrane. Between them there is a small plug of necrotic tissue, belonging to the ovum, but not adherent to the folds. To all appearances we have here a perfectly normal tube wall without any indication of inflammation or any clinical signs of any infectious disease. For some unknown reason the ovum became lodged in the tube, burrowed into the tube lumen in both directions that is, towards the uterus and towards the abdominal wall. Considerable change has taken place in the ovum, as it can hardly be considered normal for this stage of development. The coelom is very small in a transverse direction and has become elongated to correspond somewhat with the shape of the surrounding clot. The embryo is located in the implanted region, but the ovum is drawn out into the clot on its distal side, being fairly well constricted in its middle; that is, there seems to be a tendency for the chorion to be divided into two parts. The inner part contains the normal embryo, and the outer a small isolated body which seems to be a part of the umbilical vesicle. At any rate, the structure is identical with the umbilical vesicle, but it is not connected. So far as external form is concerned the embryo appears to be normal. The organs are sharply defined and the surface is beautifully molded. Sections show that the embryo is normal, except the ventral half of the thoracic spinal cord, which has become dissociated. (See plate 1, fig. 4, and plate 11, figs. 3 and 4.)
The villi of the chorion of No. 808 are unequally divided. On one side, near the tube lumen opposite the implantation, the bare chorionic wall is separated from the lumen by the necrotic plug spoken of above. Opposite this, near the broad ligament, a large tuft of villi reaches into the tube on the uterine side and is well implanted. In the distal end of the clot most of the villi are degenerating; but strands of trophoblast remain intermingled with leucocytes and fibrin. The mesoderm of the villi forming the tuft appears to be normal and contains within it blood vessels filled with blood from the embryo. The tips of the tuft of villi are filled with great masses of active trophoblast, which often radiate in strands to the tube wall and invade it. These are accompanied in places with fibrinous strands, which are more or less filled with leucocytes. Many of the villi are encircled with lakelets of blood which contain no fibrin, indicating that it is not coagulated. It seems as though the trophoblast secretes some substance to prevent coagulation. At points the cells of the trophoblast and of the tube wall are so intermingled that it is practically impossible to make a separation; the trophoblast cells, however, surround the small lakelets of blood, producing an appearance of cavernous tissue. This is especially well marked at the tips of the villi. It appears as though the trophoblast has tapped all the veins of the tube wall, and because there is no formation of a decidua it is impossible for the wall which is thrown up to prevent excessive hemorrhage. We have here a true intervillous circulation which, if not arrested, is bound to destroy the ovum. In this specimen, as in all the rest, there is no decidua. In fact, to describe a decidua in them would be a stretch of the imagination. Within the tube wall there are numerous leucocytes, just as we have in a normal implantation.
We can here describe several varieties of trophoblast :
- The ordinary kind composed of quite uniform cells stacked upon the tips of the villi.
- The longer streams of trophoblast which radiate from the villi throughout the clot and along the fibrin bands which are also present.
- Trophoblast cells scattered either within the muscle wall of the tube or through the clot or upon the surface of the clots. These are no doubt the cells pictured by Bryce and Teacher in their Plate VI. However, these writers are of the opinion that these are decidual or maternal cells, but they occur with much regularity at the tips of the villi where they come in contact with the clots. They spread first from the villi as solid strands and, as they spread, the cells become separated, but do not come in contact with maternal tissue. They are like the pickets in advance of an army. First they appear in every respect like trophoblast cells, and, as they are always connected with them, I think the statement is warranted that they belong to the trophoblast and are in no respect decidual. The fact is that decidua can not be demonstrated in tubal pregnancy, unless indeed we describe the trophoblast as such. This point, however, can not be determined when the trophoblast cells have invaded the maternal tissue.
- The syncytium seems to be present where there is great activity.
- A peculiar kind of syncytium which forms a network, or, to describe it better, is vacuolated. There are all stages of gradation between the solid and vacuolated varieties. The large masses of solid trophoblast usually appear to be located upon the villi. These run out into the processes which radiate in all directions, encircling other fresh blood cells. At about this stage of development numerous clear vacuoles are seen in the solid mass of syncytium. These become larger and larger, blending with the processes of adjacent syncytium, thus forming a curious network as shown in plate 1, figure 3. This type of trophoblast seems to be most pronounced where there is great activity, i. e., when the tube is being eroded. It appears to throw up a dam to prevent excessive hemorrhage or to engulf the blood escaping from the freshly tapped blood vessels. In fact, the vacuoles are filled partly with healthy, partly with disintegrating blood corpuscles, and partly with a clear fluid. The dam thus thrown up makes a sieve through which the blood percolates on its way to destruction. Is it not probable that in this way pabulum is formed for the ovum? (See plate 1, fig. 4.)
The vacuolated syncytium seems to be identical with the variety of trophoblast called plasmodium by Bryce and Teacher. This is well shown in their Plate V. It can also be recognized in the illustration by Peters; for example, in his figure 14, Plate VI, and again by Jung, figure 19, Plate VII.
In the lakelets between the large strands of syncytium the red blood corpuscles are well formed and sharply defined, but as the blood comes in closer contact with the trophoblast we see all stages of disintegration. They break up into small granules, the finer of which do not stain so intensely as blood and often run together in large masses, which sometimes in the neighborhood of syncytium are easily confused with it. Many of the granules in properly stained specimens are intensely red, much more so than normal corpuscles. These may be seen within the protoplasm of the syncytium and sometimes within the vacuoles, and often within ordinary trophoblast cells. The minute granules, which stain intensely red, vary in size, but are usually about as large as the chromatin of the nuclei, though they often fade off into the ultramicroscopic. Especially is this so in the neighborhood of the masses which are easily confused with the syncytium. It appears, then, that the corpuscles first break down into intensely staining granules, which are partly taken up by the cells and partly undergo further transformation in a homogeneous mass. The description here given rests upon specimens which have been counterstained in eosin, aurantia, and orange G, one of which is shown (plate 1, fig. 4).
The chorionic wall in No. 808 is for most part quite thin and at points it seems to be ruptured. In the region of the embryo the mesoderm of the villi is quite normal, being composed of delicate fibrillse arising from the tips of the multipolar cells. Scattered throughout this tissue are numerous large cells with a delicate protoplasm, which usually takes on some of the counterstain. These are the Hofbauer cells, so frequently seen in pathological villi. Some distance from the embryo the villi are mostly fibrous and are undergoing all sorts of degenerative processes; that is, they are dying.
The coelom is long drawn out and fully constricted at one point to correspond with the shape of the chorion. In the neighborhood of the embryo it is entirely filled with the amnion, but in the small spaces between the amnion and the chorion is a granular deposit containing numerous maternal red blood corpuscles. As these are embedded within this granular mass, they must have lodged there while the specimen was still living. There are also numerous nucleated cells in this region which appear to have wandered from the embryo.
There are also two varieties of magma found within the coelom. On the uterine side of the embryo is a peculiar flaky granular magma which takes on a blue tinge in hematoxylin. The larger flakes are stratified and show alternating lighter and darker zones encircling a central highly stained granule. Occasionally this type of magma is found in other specimens, but the flakes are often very irregular and some of them stain intensely with hematoxylin. On the outer side of the embryo the coelom is filled with a dense reticular magma. Within this is a large space containing the isolated yolk sac spoken of above. The fibrilke of the magma stain intensely in the Van Gieson stain.
In sections made in this way it is clearly seen that the magma is composed of a dense network of fibrils. This network reaches through the chorionic membrane to this epithelial covering and bears a distinct relation to the mesoderm cells; in fact it belongs to them. As the mesoderm cells do not always form any marked border around the coelom, but reach into it, they carry with them a denser network of fibrils, showing that the protoplasm immediately around the nuclei is composed of very highly differentiated magma fibrils. In other words, magma fibrils are coming out from the cells of the mesoderm and projecting into the ovum. This observation is fully verified in the pathological ovum of No. 402, in which the individual magma all arises from the mesoderm of the chorion and radiates into the cavity of coelom. In the pathological magma of this specimen the fibrils are as highly differentiated in the coelom as are those immediately surrounding the nuclei in the normal specimen, No. 808.
The necrotic plug between the ovum and the tube wall is very pronounced. It is about 1 mm. thick and 2 mm. wide. Towards the distal end of the tube it thins out and it is probable that this thinness occurs at the point of rupture of the ovum from the tube wall into the tube lumen. The plug itself is stratified, as it is composed largely of fibrils. To the naked eye it appears like a lens. No doubt it represents a similar plug which is formed in the uterus when the ovum implants itself normally.
Normal Embryos 6 to 9 mm in Length
To all appearances the ovum of the embryo, 4 mm. long (No. 808), is well attached to the tube wall, but it is impossible to state definitely whether the attachment is normal or even whether the ovum is normal, as I do not possess suitable stages which have been studied from this standpoint for comparison. One thing, however, seems to be evident, namely, that there is an excessive amount of blood between the villi of the chorion and that the shape of the chorion is normal. The specimens succeeding this (Nos. 706, 612, 597) contain embryos apparently normal, ranging from 6 to 9 mm. The external form of the embryos appears to be normal, but only one of these (No. 612) was cut into serial sections. In general the embryos of these specimens have been more or less injured, which makes it difficult to pass upon their normality. In all three of these specimens the chorionic wall is very hemorrhagic. In the first specimen (No. 706) the hemorrhagic mass is the size of a walnut. It contains within it an amniotic cavity just large enough to hold the embryo, which is 6.5 mm. long. The villi of the chorion show marked degenerative changes, but at some points the trophoblast is active. The chorionic wall appears to be somewhat fibrous, but is rich in blood-vessels. In the sections the exocoelom contains a dense reticular magma through which both embryonal and maternal blood cells are scattered. Upon the wall of the chorion are several dense plaques of trophoblast, more especially evident at places where the chorion comes in contact with fresh blood. We have here a specimen which to all appearances is pathological. The hemorrhage is so extensive, the blood clot is so thoroughly organized, and the amniotic cavity is so very small, that it is surprising that an embryo, normal in appearance, should be found within it. Most of the tissues are quite active and certain groups of trophoblast cells appear to be normal; otherwise, the villi are degenerating. It appears, then, that only a few villi are necessary to nourish the ovum properly.
In the next specimen (No. 612), the changes of the chorion are not so pronounced. The chorionic wall is very vascular and unusually fibrous for one containing an embryo so small. The amnion is also well formed and in apposition with the chorion. The villi are well developed and upon their tips is a very extensive trophoblast. At some points are large areas of vacuolated syncytium. The trophoblast comes in close contact with the tube wall and is partly separated from it by remnants of its epithelial lining. To all appearances the implantation is normal with an exceptionally large amount of organized blood clot between the chorion and the tube. We have here an excellent example of an ovum, well nourished despite the fact that the intervillous spaces are entirely plugged with blood clot. The villi have perforated this clot and are well attached to the tube wall. The clot is stratified, that is, it is composed of alternating layers of fibrinoid tissue and blood, and it is also well infiltrated with leucocytes. At points where the villi are dying the leucocytes form large colonies. The trophoblast within the clot has also a peculiar appearance, the great amount of hyaline matter between the individual nuclei making it look like cartilage. At any rate, the changes are so pronounced that we can not possibly look upon the clot between the villi as forming a normal circulation. We have really a red infarction through which the villi extend to get their nourishment from the tube wall.
Specimen No. 597 contains an embryo 9 mm. long, which appears to be normal. It is encircled by a narrow zone of blood which is not organized, but within which there are many necrotic villi. There are also marked signs of inflammation and a little active trophoblast. There is some vacuolated syncytium, undergoing necrosis. It is quite difficult to understand why a specimen like this should contain a normal embryo. Possibly the embryo had been dead for some time, as its tissues are soft and there were extensive necrotic changes in the chorion. We appear to have here, in the specimens just described, stages of degeneration of the ovum with embryos up to 10 mm., showing partial or complete destruction of the chorion and the ultimate death of the embryo. The embryo 4 mm. long was undoubtedly alive at the time of the operation, and the embryo 9 mm. long was undoubtedly dead. Between these two extremes we have a gradual increase of the amount of blood between the villi, which ultimately detaches the chorion from the tube wall and causes the death of the embryo. This condition, which should be viewed as a true intervillous circulation, seems to prove fatal for the embryo. In the tube such a condition must end in the destruction of the ovum and in the uterus in an abortion. Unless the activity of the trophoblast is sufficiently pronounced to destroy the masses of blood which become lodged between the villi and at the same time prevent further hemorrhage into these spaces we can hardly expect a normal implantation. From all appearances the development of the chorion of No. 612 is such that we could have expected the further development of a normal embryo in case the tube had not been removed by the surgeon. There is a beautiful, active, vacuolated syncytium which forms a pretty complete wall around the intervillous clot. This wall is sufficiently solid to prevent any great amount of new blood from entering these spaces. The trophoblast is growing in among the muscles of the tube wall and it is also to be seen in many of its blood-vessels.
Normal Embryos Over 9 mm Long
A more advanced stage is seen in a similar specimen (No. 109) which contains an embryo 10.5 mm. long. This also shows a considerable amount of blood between the villi, but most of it seems to be fresh. A portion of the clot is stratified, but the rest does not show any marked signs of coagulation. Part of the stratified clot has within it a group of leucocytes. The chorion appears to be normal, and where it comes in contact with the tube wall its trophoblast is extremely active. It forms a wall which prevents further hemorrhage from the vessels of the tube into the intervillous spaces. Various stages of this process are shown in the figures of this specimen. In plate 1, figure 2, the trophoblast within the sinuses is shown. Most of the endothelial lining of the veins has been destroyed, but part still remains, as shown in the figure. An earlier stage of this process of destruction of the wall of the blood vessels is shown in plate 1, figure 1. Here are found all stages of trophoblastic development, from the tips of the villi to the free cells within the blood vessels. A somewhat more advanced stage is shown in plate 1, figure 3. The wall of the venous sinus has been completely destroyed and in its place are strands of trophoblast. Between the lumen and the villi is a pronounced vacuolated syncytium partly filled with blood. This specimen illustrates beautifully the dam thrown up by the trophoblast to prevent hemorrhage from the open veins. The blood between the villi is well encircled with trophoblastic cells; at some points the leucocytes have invaded it. A large clot, which is about 15 mm. long and 2 to 5 mm. thick, separates in part the chorion and the villi from the tube wall. On the chorionic side it is covered with an incomplete layer of trophoblastic cells, as shown in plate 4, figure 3. These seem to be invading the blood clot. Individual cells are often found far from their main strand, as shown in this figure. Undoubtedly we have here a clot of blood which the trophoblast is attempting to destroy. There is no indication of fresh hemorrhages in any of the sections. The trophoblast is extensive and vacuolated, forming a wall which protects nearly all of the intervillous spaces.
An even more perfect specimen of implantation is possibly that of No. 670. The embryo in this case was 12.5 mm. long and the spaces between the chorionic wall and the tube wall are largely empty. There are, however, several hemorrhagic areas about 5 mm. in diameter. Where the villi come in contact with these there is a marked layer of fibrinoid necrosis, a sample of which is shown in plate 2, figure 3. It appears as though this substance may arise from all kinds of tissue, either maternal or embryonal. In the figure just referred to it seems to rise from degenerate trophoblastic cells. In this case we seem to have the reverse of the process shown in No. 109. There the trophoblast is destroying the blood clot. Here the blood clot is surrounding the zone of necrotic tissue which is composed partly of trophoblast. Elsewhere in this specimen are large strands of this fibrinoid substance, which often reach into the tube wall. In general, however, the trophoblast is extremely active and markedly vacuolated. Where the trophoblast is heaped up into large islands, their centers are often necrotic, forming yellow nodules, which in turn are being invaded by vacuolated syncytium. This condition is often seen in uterine implantation and has been described and pictured by Grosser. Undoubtedly we are here dealing with the normal destruction of less-favored villi. Adjacent to one of these masses are several villi, which are being invaded by their own trophoblast. This condition is very pronounced in this specimen and is well illustrated in plate 2, figure 7. In this same figure numerous Hofbauer cells are seen It would seem possible that these Hofbauer cells are free trophoblast cells within the mesoderm of the villus, an opinion already expressed by me in my paper on monsters. As in No. 109, we have here a beautiful case of successful implantation in the tube. There are but few hemorrhages in the intervillous spaces, the trophoblast is extensive, and the villi appear to be normal. In this case we also have a normal embryo. In contrast with these two specimens, No. 535 contains a normal embryo 11 mm. long, and shows an extensive intervillous hemorrhage. There are some slight changes in this embryo; the branchial arches are partly obliterated, and the body wall is sufficiently transparent to allow the ribs to be seen, so that in all probability the embryo was dead before the tube was removed. In this case the tubal mass is very large, about 55 mm. in diameter, and the tube wall is thick, dense, and hemorrhagic, measuring about 15 mm. Within this hemorrhagic mass all stages of degeneration of villi can be noted; plaques of white necrosis alternate with fresh hemorrhages. Scattered through the mass are strands of leucocytes encircling the ovum that is, at its juncture with the tube wall, a marked infiltration with leucocytes can be noted. The inflammatory process is quite extensive and the necrosis of the villi and its trophoblast is quite complete. We have here an example of the effect of intervillous hemorrhage upon the ovum. It appears to cause its destruction.
The next older stage, which seems to be of value as regards the nature of implantation, is seen in an embryo 17 mm. long (No. 676). This appears to be normal and the ovum had been peeled out of the tube before it came to us, so that it was impossible to make a careful examination of the tube wall in its relation to the villi of the chorion. We determined that the embryonic cavity was lined with a clot and sections of this clot show that it was perforated with normal villi which were covered with an extensive trophoblast. None of the sections, however, showed the trophoblast in its relation to the tube wall. The only definite point gotten from this specimen is that we have a normal embryo in an apparently normal chorion which has been peeled out of a hemorrhagic bed.
There are three good specimens with embryos, ranging around 25 mm., in which the implantation of the ovum can be studied to advantage. The first (No. 790) contains what may be regarded as a normal embryo about 20 mm. long. This specimen was no doubt alive at the time of the operation, and its surface had been attached to the side of the embryonic cavity by means of a stitch. The attachment of the umbilical cord had not been destroyed, so that it was relatively easy to get suitable serial sections. The wall of the cavity is somewhat hemorrhagic; it contains numerous hyaline necrotic patches and has attached to it the tips of the villi. There is a marked inflammatory reaction. The villi of the chorion are fibrous and tipped off with trophoblast, which often form masses with necrotic cores. The trophoblast enters the tube wall and there is diffused among the muscle bundles. It often encircles and permeates the venous sinuses. The accompanying strands of cells show a considerable amount of hyaline degeneration, which gives to the sections a cartilaginous appearance. Here we have a peculiar attachment of the trophoblast without any marked intervillous hemorrhage.
No. 657 contains an embryo which appears to be normal. It measures 25 mm. in length, is unusually white, and has a very delicate umbilical cord, which may have been injured at the time of the operation. The entire mass has been preserved in formalin, which did not penetrate to the embryo very quickly, a fact that may account for its appearance. Otherwise, the specimen seems to be normal. The amniotic cavity is especially well defined and sections of the chorionic membrane show a normal structure. The spaces between the chorionic membrane and the tube wall are filled with a spotted mass composed of old fibrous strands and fresh hemorrhages. The villi traversing this zone are largely necrotic, but some of them appear to be perfectly normal. The trophoblast covering some of these villi is active, but as the muscle wall of the tube has for the most part been destroyed, it has had no place to implant itself. It seems to have found nourishment in fresh hemorrhages right under the tube wall. At any rate, at this point the trophoblast is active and appears to be normal. Most of the hemorrhagic mass is filled with necrotic villi, showing that an intervillous circulation, when present, strangulates the villi. Only a few of those which perforate this mass freely and have an opportunity to grow again on the tips seem to survive. These no doubt are the ones which have served to nourish the embryo (plate 7, figs. 1 and 4).
The last specimen of this group (No. 183) contains a normal embryo, 28 mm. long. In general the relation here is identical with that found in No. 657. There is a large quantity of fresh blood between the chorionic membrane and the muscle wall of the tube. The space, which is here distended to a maximum, contains dead villi and large necrotic masses of trophoblast. At certain points tufts of the villi pass through this mass and reach the tube wall. Here the trophoblast is very active and vacuolated and ramifies among fresh blood. The tissue of the folds of the tube wall which also enter the clot are also dissociated; that is, they disappear by histolysis. At another point a tuft of villi reaches to the tube wall and there the trophoblast cells mingle with the tissues of the tube wall. At their tips is an extensive vacuolated trophoblast, the lakelets of which are partly filled with fresh blood. No other specimen better demonstrates that the trophoblast feeds upon a small quantity of fresh blood, but that a large quantity of older blood can not be assimilated by it. It attacks such clots as do the leucocytes. It is only when the trophoblast receives small quantities of fresh blood that we can view its relation to the tube wall as normal.
The last specimen, containing a normal fetus, whose implantation I have had an opportunity to examine, is No. 484. It contains a fetus 96 mm. long. The placenta is partly filled with a large hemorrhagic mass, within which many villi are necrotic. Between these masses there are tufts of villi, often 20 mm. in diameter, which reach to the tube wall and are intimately connected with it. At the point of juncture between the trophoblast and the tube wall is a considerable amount of fibrinous tissue. This the trophoblast invades or perforates and reaches to the blood vessels of the muscular layer, which are tapped, so that we have long strands of trophoblast reaching from the tips of the villi to the blood vessels; but here also there is very little blood between the villi. Between the villi in this region are numerous masses of necrotic trophoblast that have largely undergone fibrinoid degeneration; otherwise we have here a picture practically identical with that obtained from the uterus at like stages of development. It does not differ materially from the condition shown in Grosser's figures 124 and 131, from specimens a little older than No. 484.
Conclusions Regarding Normal Implantation
The conclusion drawn from the study of normal implantation in the tube is that in the early stages most of the ova are destroyed by the hemorrhage which is produced for their nourishment. If the dam built up by the trophoblast is sufficient to check the flood in part, enough villi will remain to nourish the ovum. Throughout development such a catastrophe is imminent, and we may have a destruction of the ovum at any time. When the tube ruptures into the broad ligament, the space for the chorion becomes sufficiently large for new villi to grow and attach themselves. If there are enough of these, an occasional hemorrhage will not impair their development. In all cases the ovum within the tube is at a decided disadvantage because it does not have a decidua to aid in producing a normal implantation. Whether this point is of much importance in the second half of pregnancy can not be answered at present. I am rather of the opinion that the decidua is of the greater moment at the beginning of uterine pregnancy.
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Cite this page: Hill, M.A. (2021, April 14) Embryology Book - Contributions to Embryology Carnegie Institution No.1-3. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Contributions_to_Embryology_Carnegie_Institution_No.1-3
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