Paper - A study of the causes underlying the origin of human monsters 11

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Mall FP. A study of the causes underlying the origin of human monsters. (1908) Jour, of Morphol., 19:

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1908 Mall TOC: Historical | Double Monster | Lithium embryos | Salts of potassium and heart | Spina bifida and anencephaly | Cyclopia and club-foot | Pathological ova | Twin pregnancies | Unruptured tubal pregnancies | Ruptured tubal pregnancies | Amnion Destruction | Moles | Pathological ova umbilical cord and amnion | Second week | Third week | Fourth week | Fifth week | Sixth week | Seventh week | Eighth week and older | Specimens and figures | Plates | Historic Papers | Franklin Mall

A Study Of The Causes Underlying The Origin Of Human Monsters

Partial on Complete Destruction or the Amnion, leaving the Umbilical Vesicle

One of the first changes seen in early human embryos is a destruction of this important organ, the amnion, which develops shortly after the umbilical vesicle is formed. We can now picture to ourselves pretty well the formation of the amnion from the epithelium of the chorion if we blend the observation of Selenka upon I-Iylobates with the very young human ovum described by Peters. About the time the ovum reaches the uterus, when it is less than 3 mm. in diameter, and after the coelom begins to form there must be an invagination of ectodermal cells into the stem of the vesicle within. A portion of the cells of this sac gives rise to the ectoderm of the embryo and the rest becomes. the epithelial lining of the amnion.


It is easy to conceive that any change in the environment which influences the growth of the ovum would first make itself felt at the very apex of the growth, and in the early stages of development this is in the amnion, including also the ectodermal plate.


At this early stage, probably during the second week of pregnancy, the three primary layers have established themselves well in their capsule of decidua, which must give nourishment to all sides of the ovum through the syncytium and young villi. In looking through sections of young ova one cannot help but think that the syncytial cells form the aggressive elements which eat themselves through everything that comes before them and cause the mucosa of the uterus to respond at once. Hernorrhages naturally follow such an action, and, judging by the frequency free blood is found between the villi, it appears that in all cases the blood comes in direct contact with the syncytium, which then grows so much the better. This vigorous layer of cells no doubt nourishes the layer of mesodern below it, which in turn cares for the embryo, for at this time there is no vascular system to carry the food from the mother’s blood to the embryonic disc. The villi which are growing so rapidly must cast some of the fluid within their mesenchyme into that of the main wall of the chorion as it splits into two layers to form the coelom. Thus, for a time, even after the blood—vessels are formed in the umbilical vesicle, the nutrition of the embryo passes through the coelom exclusively. The first blood-vessels to the embryo hasten the process from the umbilical vesicle, and it is not until the heart is formed and the vascular system has reached the villi that the nutrition passes in through the umbilical cord. This does not take place until the embryo is fully 1.5 mm. long, i. e., in the specimens of Eternod and Graf Spec. From now on the amnion begins to expand, at first very slowly and later much more rapidly, and gradually obliterates the exocoelom. This is complete by the time the ovum is 45 mm. in diameter and the embryo is 20 mm. long.


About the time the blood—vessels are formed and reach the embryo an interference in the nutrition of the embryonic mass naturally results in the destruction of the anlage of the amnion and embryo, leaving only the umbilical vesicle, which may be found either attached to the chorion or lying free in the coelom.


During this period, while the coelom is relatively very large, a disturbance in the transmission of nutritive substances from the decidua to the embryo is marked by an increase in the reticular magma of the coelom. This delicate reticulum was first described about a century ago and is pretty well marked in normal ova. As the amnion expands to fill the coelom the magma reticulé is gradually pushed before it and often remains for a time as a delicate layer between the amnion and chorion. When the embryo and amnion are more or less destroyed the magma reticulé gradually becomes denser and denser, encircles the umbilical vesicle and fills the coelom. In case the amnion is still intact but does not fill the cavity of the chorion entirely, pathological ova are usually marked by a mass of dense magma in the exocoelom. This change in the structure of the magma is so well pronounced in early pathological ova that specimens which are believed to be normal on account of a perfect villous covering are at once recognized as being diseased as soon as they are opened.


The nature of the magma is not known. I have made numerous tests with Weigert’s fibrin stain, but in no case did the fibers take on the color. Neither do they appear to be related to ordinary reticulated tissue, which is present in the embryonic state in the mesoderm of the chorion, for they are not connected in any way with the p1‘otopl'éi'$ria of these cells.


As the magma reticulé becomes more pronounced in pathological specimens it is often converted into, pr is intermixed with, a granular substance which may be termed the granular magma. In case the ovum grows to be large, as is specimen No. II5, the reticular magma is often destroyed, leaving only the granular substance, more or less mixed with fluid to fill the coelom. In older specimens we often see the cavity of the amnion filled with a mass of granular magma, while the surrounding eoelom is filled with reticular magma. However, stained sections show this separation only in a general way, for there is always more or less mingling of these two substances.

Table I. Normal Embryos

or rm: Fmsr AND Srzcoma WEEKS. '3 E! o Specimen. Embryo. Ovum. é” é’ mm mm. days Peters* . . . . . . . . . . . . . .19 1.6 x .9 x .8 3o

Merttens . . . . . . . . . .. 3x2 21
Breuss . . . . . . . . . . . . .. 5 38
Reichert . . . . . . . . . . . . . 5.5 x 3.3 42
Siiggnbeck van Heueom . . . . . . . . . . . .. .325 5.5x4.5
Graf Spee . . . . . . . . . . . .37 7. x 5.5 5 wks.
No.11 . . . . . . . . . . . . .8 1ox7x7 41
Keibel . . . . . . . 1. 8.5x7.7x6
Eternod . . . . . . . . . . . . 1 1.3 10.8 x 8.2 x 6 34
Graf Spee . . . . . . . . . .. 1.54 1ox8.5 x6.5 5 wks.
No. 71 . . . . . . . . . . . . .. 1ox9x5 4o
No. 361..... . . . . . . .. IOXIOXIO 41
No. 250 . . . . . . . . . . . .. 2. Iox9x8
No. 384 . . . . . . . . . . . .. 2. r6x13x re 49
No. 391 . . . . . . . . . . . .. 2. 16x14xr2 42


References are given in my article in the Johns Hopkins Hospital Reports, Vol. IX, 1900.

With this introduction to the primary changes in very young pathological ova we are ready to discuss those cases in which the amnion and embryo are destroyed, individually and in groups. In order to make this easier I have brought the specimens together in Table II, giving certain important data. Table I includes all of the normal ova I have been able to collect from the literature and is to be used for making com—. parisons. By comparing the two tables it is noticed at once that the pathological ova are older and larger than the normal ones. But, judging by the changes within, it is highly probable that these began some time before the second week of pregnancy. If their ages are estimated by the size of the umbilical vesicles they would range themselves from one to six weeks, during which time the vesicles grow from one to six millimeters in diameter. However, if we consider each millimeter in diameter as indicating a week in age, we again get into trouble when this is compared with an arrangement according to their ages as determined by their last menstrual periods. It seems to be safer to assume that the pathological changes in these specimens began during the first and second weeks of pregnancy, and that the chorion continued to grow while the vesicles within became larger in some cases and smaller in others. Had the changes in them begun as late as the third week, when the amnion is sufficiently developed to remain and continue to grow, entirely different specimens would have been obtained, as will be shown later on.


Table II. Vesicular Forms of Pathological Ova
No. Ovum. Vesicle. M752: 1 Amnion. Choi-ion, mm. mm. days 13 8 x 7 1,4x6 Formed Fibrous and partly covered with villi. 3o4 15 x 7 x 6 2 " Chorion normal, but decidua infiltrated with leucocytes. 158 12 x 6 2 “ Atrophic. Tubal pregnancy. 143 25x10 “ Normal. 1 1 1 o x 7 x 7 1 . 5x1 4 1 Partial Covered partly with villi. 396 7 2x1 5o “ Somewhat fibrous and invaded by syncytium. 134 17 X 1 1 3x9 33 “ Normal. Embryo infected with mother's blood. 58 2ox18x12 6 71 “ Fibrous. 87 24x16x9 2.5 42 “ Normal. 24 21 x 16 X 5 2.6 Multiple Syncytium increased. 78 36x33x13 1.6 87 “ Atrophic. 247 4o x4o x r7 2.5 " Nearly normal. 21 12 x 9 x 5 5.5x3.5 None Some magma reticulé in coelom. 13o 15 X 10x6 4x3x1.5 I4 “ Normal. See Table IV. 123 17 x 14 2xr.5 27 “ Irnbedded in pus. 18o 2o x 15 x 10 1.5 37 “ Fibrous. In a mucoid mass

rich in leucocytes.

58 “ Fibrous. Few villi with pus. “ Thin and fibrous. No villi.

“ Very fibrous. Few villi.

264 25x2ox15 2 14 3o 1. I47 3OX27X2O I

moi


  • The age of the embryos is given according to His. Since writing the above I have come to the conclusion that he has underestimated


Amnion formed. — One of the earliest specimens of vesicular forms in which the amnion is present but the embryo is pretty well destroyed is No. 13. There is much magma reticulé in the coelom. It is quite clear that the double vesicle represents the amnion and umbilical vesicle, which are bound together by a mass of mesoderm. This contains two bloodvessels, which unite at the point where the mesoderm passes over into the chorion. There are no other structures of the embryo present. The tissues have become dissociated, the mesoderm cells are round, and other round cells are in -the cavity of the yolk sac. In general, we have the remnants of an embryo a little younger than Eternod’s with the bloodvessels reaching to the chorion.

An excellent specimen, No. 304, which was cut into serial sections with the entire chorion and decidua, is most instructive. The villi of the chorion are normal in shape and are covered with a very active syncytium. They contain remnants of blood—vessels within them, showing that at one time there was vascular connection between the yolk sac and the villi. The decidua is encircled and infiltrated with leucocytes and between the villi there is a mucoid mass rich in leucocytes, showing that the inflammatory process has reached the ovum. The coelom is well filled with magma reticulé, in which there is imbedded the umbilical vesicle attached to the remnants of the embryo. This is partly covered with the amnion, which runs out into a stem, containing an allantois, the latter not connecting with the chorion. There are remnants of a nervous system and numerous blood islands in the yolk sac, but no heart.

This specimen corresponds well with No. I 3 and gives, in

them, by about ten days for embryos less than 22 mm. long. For embryos from 22 to 33 mm. long I believe his estimations fairly accurate. To make the prop'er correction it would be necessary to recast all of my tables and much of the text. The reader may make them by adding ten days to the age of embryos less than 43 days old. My new data, about 1,000 in number, relating to the age of human embryos will be published in Keibel-Mall’s Handbuch der Entwicklungsgeschichte early in 1909. No. 1.] ORIGIN OF HUMAN MONSTERS. 75

addition, the changes in the decidua which caused the difficulty. The equilibrium between the chorion and embryo was overthrown at about the same time as in No. 13 and the magma became more pronounced than normal. The tissues then became dissociated, and on account of lack of nutrition they began to disintegrate.

The next specimen (No. 158) which belongs to this group is of about the same age, judging by the size of the chorion. It is from a tubal pregnancy and is interesting because there are no villi upon the chorion. The main wall of the chorion is somewhat fibrous and there are but few epithelium cells upon it; these come in direct contact with the lining epithelium of the tube. The nodule within is as a double sac, partly joined by a clump of cells, which runs out into a long process containing a blood-vessel (?), but does not join with the chorion. The whole mass appears necrotic, at least it does not stain well, and probably represents the amnion and yolk sac, which come to a sudden end due to the radical changes in the chorion.

The fourth specimen (No. 143) which may be included with this group is unique, for within a normal chorion there is a double vesicle much larger than the umbilical vesicle ever becomes during development. However, the specimen had been in alcohol for a long time, and the cells are mostly destroyed, due to bad preservation. The two sacs, which do not communicate with each other, are of the same structure as the mesoderm of the chorion, to which they are bound by a strong pedicle.

Amnion partly formed.—The five specimens in this group, Nos. II, 396, I 34, 58 and 87, are most interesting, and have caused me much trouble. Four of them were considered in the first communication and need only be reviewed in this place in order to make the chain of events complete.

No. II was first described as a normal embryo because its chorion and apparently all of its tissues were normal. The embryonic mass, however, communicated freely through a rounded and natural opening with the coelom. Furthermore, I 76 MALL. [VoL. XIX.

had every reason to believe that the abortion was produced through mechanical means, a circumstance which I have since learned does not insure a normal embryo. When I received the specimen (I893) sketches of it were submitted to Professors Minot and Graf Spee, who discussed it quite extensively in their letters to me, and they both felt that more young specimens would have to be studied before this could be properly interpreted. Professor His, however, to whom the sections were shown, was inclined to think the embryo normal, and as such it was first published. At present it seems to me that the ovum was normal until the woman “sprained herself six days before the abortion.” The sprain was followed by a flow of blood each day until the abortion occurred. Thus it happened, it seems to me, that the chorion grew large and the villi small; certainly they are not as well developed as in the other young ova given in Table I. Through some means, possibly mechanical, the amnion became torn and the ectoderm spread itself partly over the coelomic side of the yolk sac and belly stalk. The amnion in Peters’s ovum is very delicate at one point, being composed of but a layer of ectodermal cells, and in Van Heukelom’s there appear to be actual openings in the amnion. With these facts before us, it is not remarkable that a break should occur at this point occasionally.

Another very valuable specimen is No. 396, which was obtained from a tubal pregnancy. VVithin the coelom of the ovum there is a double sac, one of which is clearly the umbilical vesicle, and the other may represent the amnion and embryo. What is especially interesting in this specimen is the relation of the umbilical vesicle to the chorion. At a number of points they come in contact, are adherent, and the bloodvessels from the umbilical vesicle pass directly over into the chorion, from which they spread into its villi. This specimen proves that the presence of blood—vessels in the chorion is not dependent upon the development of the body of the embryo. They may grow to it in a direct way.

A third specimen (No. I 34), much like No. II, also obNo. 1.] ORIGIN OF HUMAN MONSTERS. 77

tained from a criminal case, is equally remarkable, for we have here the amnion communicating with the coelom. In this case the ovum had been punctured by a bougie and the coelom filled with mother’s blood. The clot is very recent, for it is composed largely of well-formed red corpuscles. A portion of it is composed of many leucocytes, and where they come in contact with the embryo the leucocytes are in a very imperfect state of preservation, showing irregularities and fragmentation of their nuclei. Fragmented leucoyctes are also found througl1out the clot, in the blood-vessels of the embryo, in the chorion and yolk sac. At points in the villi leucocytic thrombi are found in the embryo’s blood-vessels, which shows the effect the tissues of the embryo have upon the leucocytes of the mother. No bacteria were found in a section stained for them. On the other hand, the tissues of the embryo are well preserved, there being no evidence of extensive necrosis. However, on one side of the yolk sac the cells have desquamated.


The bougie in puncturing the chorion probably also entered the yolk sac and was followed by its collapse. In the table its dimensions are given as 9 x 3 mm, which equal about a spherical vesicle 5 mm. in diameter.


The amnion is also torn open, and within it there are fragmented leucocytes. The invagination does not include the whole embryo, for a portion of the mesoderm covering the yolk sac contains myotomes. The experiment represented in this ovum gives us much over which to reflect.


According to the woman’s statement from whom this specimen was obtained, the menstrual period had lapsed five days before the abortion took place, and her mechanical interference took place but a few days earlier. It is difiicult to understand this high refinement in the production of abortions, and the degree of development of the ovum and embryo indicates that the specimen dates back to the last menstrual period. Possibly morning sickness, which in such cases may precede the first lapsed period, induced the woman to pass a bougie into the uterus after the period had been overdue a couple of days.


The amnion is partly within and partly upon the stem of the yolk sac in specimen No. 58. In it the mesoderm of the chorion, villi, pedicle and sac is fibrous and abnormal in appearance. It may be that in this case a portion of‘ the amnion broke out of the stem and the portion that remained developed into a small vesicle filled with beautiful epithelial cells. There are some blood islands within the stern of the vesicle. The coelom is filled with jelly—like magma and the vesicle has a granular deposit within it.


The last specimen of the group is No. 87. Here the yolk sac is imbedded in reticular magma and is not connected with the chorion. It is covered with a layer of epithelium, which at one point is invaginated. Below this layer there is a thick mesoderm, in which there are numerous blood islands. The chorion is normal. On the opposite side of the coelom there is a normal embryo of the third week with its own umbilical vesicle and cord. In this specimen we have twins, one of which is normal and the other has undergone this remarkable change, found beginning in specimen No. II.


Multiple amm'ons.—The last two embryos discussed may also be classed under this head, and they therefore represent intermediate stages between the two groups. By multiple amnions I mean two or more vesicles which arose from the original amnion located in the stem of the yolk sac.


In these three specimens, Nos. 24, 78 and 247, nothing marked is found in the chorion, excepting that of No. 78, in which it is atrophic. In this specimen the coelom was found filled with fluid; in No. 24 it was filled with a moderate amount of reticular magma, and in No. 247 with granular magma.


In No. 24 the stem of the vesicle is broad and contains blood-vessels. The endoderm of the yolk sac is well marked and from it the allantois arises and branches as it spreads, thus forming a multiple allantois. Within the stem there are also a number of sharply-defined vesicles, some of which communicate with its epithelial covering. Each vesicle appears to be a small amnion, and this condition may therefore be designated multiple arrmion. The second specimen, No. 78. is much like the one just described. Again the stem of the vesicle is encircled by a layer of epithelial cells, and within it there are a couple of vesicles lined with the same kind of cells. There are also some blood—vessels within the stem.


In the third specimen (No. 247) of this group the vesicle is detached from the chorion; it is pear-shaped and is lined with a single layer of epithelial cells. The outer layer is relatively thick, is composed of mesoderm in which are located numerous large spaces filled with blood; there are no bloodvessels in the chorion. VVithin this mesodermal layer there are a number of sharply-defined vesicles lined by a single layer of epithelial cells which is unlike that of the main vesicle. It is natural to conclude that the large vesicle belongs to the yolk sac and is lined with endoderm, and that the smaller vesicles form multiple amnions and are lined with ectoderm.


Table II shows that the age of the specimens (from Nos. I I to 78) increases with the size of the chorion. The same is true regarding the last group, Nos. 21 to 147, which is also arranged according to the size of ova.


Complete destruction of the amnion.—In the specimens just discussed it has been shown quite conclusively, I think, that radical changes may take place in the amnion and embryo of very young ova when the chorion is affected. The remaining seven specimens of this group show still greater changes in the embryonic mass, 1'. e., both the amnion and embryo are destroyed entirely, leaving only the umbilical vesicle. That it should be so, and not the opposite, is quite natural when we take the order of development into consideration. The embryo and amnion receive their nutrition in early stages from the umbilical vesicle, which in turn draws upon the fluid within the exocoelom. This in turn is acted upon by the exchange of fluid with the villi.


In these specimens (Nos. 21 to 147) it is seen that the changes in the villi are more pronounced than in those in which the effect upon the embryonic mass was not so marked and show to what extent the yolk sac can endure hardship. The degree of change is expressed pretty well by the size and age of the ova; in the younger ones (Nos. 21, I 30 and 123) the yolk sacs are simply detached, while in the older ones (Nos. 264 and I4) they are fibrous and well attached to the chorion.


The amount of magma within the coelom tells the same story. There is some in No. 21, considerable in No. 130, much in No. I23, hard and hyaline in No. 264, and completely filled in No. 147. Thus we have in these specimens the gradual changes in the umbilical vesicle after the amnion and embryo have been destroyed. No doubt some- of the earlier stages (Nos. 21 to 180) would have reached a stage similar to No. 147 had the ova not been aborted. Instead, the yolk sacs would probably have been destroyed entirely to make chorions without embryos and uterine moles. But few of them could go on degenerating for eighty-nine days, ending with an atrophic umbilical vesicle.


The first specimen of this group is composed of two vesicles with blood islands in the outer layer of mesoderm. Of course it is possible that one of these represents the amnion, but I am of the opinion that it is a dilated allantois on account of its close resemblance in structure and layers with the main vesicle. Another free umbilical vesicle is found in No. I 30. However, it‘ is uncertain whether or not this was torn away from the-main embryonic mass before or after the ovum was aborted. No. I23 is from a clear case of complete separation of the umbilical vesicle from the chorion. The ovum appeared normal, but more careful observation showed that i-t was encircled with pus. Within the coelom the free umbilical vesicle was found to have a large opening on one side, showing that its destruction had also begun.


No. 180 is another case of entire destruction of the embryo, leaving only the umbilical vesicle. The chorion contains villi and blood-vessels. Between them there is a slimy mass, in which there are many leucocytes and islands of syncytium. The growth of the syncytium appears to have been violent, and it encroaches upon the mesoderm of the chorion, which at points is beginning to be fibrous. Here also the primary trouble seems to be due to the mucus and pus-which bathe the villi of the chorion; they naturally cause havoc with the nutrition of the ovum.


The next specimen of this series (No. 264) is a very valuable one, for its tissues, from the embryo to the decidua, are unusually well preserved and the menstrual age is given. The chorion is fibrous and thickened, and between the villi there is mucus which is well infiltrated with leucocytes. The coelom is very small, but IO mm. in diameter, and is filled with 3 mass of hard hyaline magma.


The embryo is represented by a vesicle composed of two layers, the outer of which is much thickened at its attachment to the chorion. Here it is decidedly mesodermal in character and contains many large blood-vessels, filled with blood, which spread into the chorion. In the tissues around these blood-vessels there are many round cells which are similar to, and no doubt have come from, the embryo’s blood. Many round cells are also scattered through the magma.


A similar remnant of an embryo may be seen in specimen No. I4. The mesoderm is very fibrous and extends over the vesicle within. Within the chorion there are groups of epithelial cells which are no doubt derived from the syncytium. There are a few blood islands at the base of the nodule and two other spaces lined with spindle-shaped cells. The main cavity of the nodule is lined with epithelial cells, which no doubt represents the yolk—sac cavity.


No. 147 is a specimen much like No. 14, giving, however, its menstrual history, which makes it eighty-nine days old. The chorion is fibrous and partly covered with villi and the coelom is filled completely with magma reticulé. Lying in the magma, but detached from the chorion, there is a small vesicle one millimeter in diameter. One-half of the vesicle is composed of the single inner layer, and on the other there is an additional thick outer mesodermal layer, in which there are numerous blood-vessels filled with blood. There are also blood-vessels in the chorion in the immediate neighborhood of the vesicle, showing that the two were connected at an earlier period in their development.


No doubt this vesicle has gradually degenerated, but has lived so long because the blood cells are more resistant than any of the other tissues of the embryo, and, therefore, could hold the yolk sac intact more or less. However, it is clear that of the structures of the embryo the yolk sac is the last to disintegrate when the chorion is affected.