Paper - Cytological studies on the internal secretory functions in the human placenta and decidua: Difference between revisions

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#REDIRECT [[Paper - Cytological studies on the internal secretory functions in the human placenta and decidua (1921)]]
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| [[file:Mark_Hill.jpg|90px|left]] This historic 1921 paper by Fujimura is an early description of the developing placenta and the decimal changes in the pregnant uterus.
 
 
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=Cytological Studies on the Internal Secretory Functions in the Human Placenta and Decidua=
 
Gencho Fujimura
 
 
Osaka Medical College, Osaka, Japan
 
Two Double Plates (Ninety-Six Figures) and One Text Figure
 
 
==Introduction==
 
In recent times, along with an increase of knowledge on
internal secretion, it has been imagined by many authors that
in the placenta and the decidua there should exist such a function. According to the literature which I know, Lettule and
Larrier (’01) are those whose attention was first drawn to this
subject. They detected in the syncytium layer a kind of granular body termed ‘Plasmoidale Kugeln.’ This body they took
to be a secretion of the placenta. Subsequently, Veit (’O2)
attempted to trace the cause of eclampsia, and Behm (’03)
the cause of morning—sickness to the function of the syncytium,
 
and Bouchacourt (’03) observed an increase of lactation by using .
 
some placental preparations. Further, Halban, supported by
his plentiful clinical observations, stated that the swelling of
the nipples noticeable in a newborn child, the congestion and
hyperplasy of the uterus, the hypertrophy of the mammary
glands of a pregnant mother, and hypertrichosis are all probably
due to his so-called ‘Reizstoff,’ which is thought to be a product
of the placenta. Among other things, it seemed he tried to
deduce the existence of the closest functionary correlation between the placenta and the mammary glands. Since the result
of Ha1ban’s studies was published, the functions of internal
secretions likely to exist in the placenta drew general attention,
and thereafter studies of this subject followed quickly one
after the other. In the present essay I have refrained from
chronologically relating all the results of these researches,
but instead, with a view to giving only a general idea of what
is known about this subject at present, I have confined myself
to the summing up of" all the points of the investigations made
by the various authors up to now, and to dividing them intoa
few large sections along the lines of experimentation, biological chemistry, and histology. ‘
 
Now, in the early experimental investigations, it was the
first attempt of the various authors to investigate chiefly the
effect which the placenta has upon the mammary glands, and
the methods employed were either to inject into the animal
used as the subject of the experiment an extract of the placenta or to transplant the placenta, and the results in either case were
for the most part positive (Feller, ’09; Lederer and ’Pribram,
’10; Aschner and Grigoriu, ’11; Cristea and Aschner, ’12;
Basch, ’12; G. Kawaida, ’12; M. Dohi, ’l6). However, as it
was incidentally discovered at the same time that the placenta
had shown_ some strong special reaction upon the other organs,
e.g., the Vascular organs (Schickele/12), the internal secretory
glands (Fellner, ’13; Colle, ’13), and the uterus (Fellner, ’09;
Okintschitz, ’14; Hermann, ’15), it naturally became difficult
to assert that the ingredients of the placenta have such properties as react upon the mammary glands alone. And, further,
as it became known generally that such changes in the mammary
glands as mentioned above were not only due to pregnancy or
the placental ingredients, but were also caused by extracts of
the various organs, such as the embryo (Mandle, ’05; Bayliss
and Starling, ’06; Foa, ’10; Biedl and Konigstein, ’ 10 ; Aschner
and Grigoriu, ’10), the ovary (Ott and Scott, ’10,' Aschner and
Grigoriu, ’11; Frank and Unger, ’11; Hermann,’ 15; Y. Taniguchi, ’16), the pituitary body (Hofstatter, ’11), the pineal and
thyreoid glands (Ott and Scott, ’1l),the uterus while in childbed and the mammary glands which are giving suck (Schoefer
and Mackenzie, ’11), the intestines, the testicles, the spleen,
and the thymus (Kehrer, ’15), the decidua (Gentili and Binaghi, ’17), as well as by a certain kind of chemical matter, such
as ‘Lymphagoga’ (Aschner and Grigoriu), and albumin, too
(Frank and Unger, ’11; Fraenkel, ’14), the theory of internal
secretion in the placenta which had begun to be adopted generally for a time began to lose its value by degrees.
 
In the next place, along lines of biological chemistry, there
are the researches made by such authors as Higuchi (’09),
Hermann (’15), and Harada (’16). These authors extracted from
the placenta various kinds of chemical matter as its principal
ingredients and subjected them to close examination, but they
never mentioned a ‘hormone,’ which is always existent in the
placenta.
 
Thirdly, with regard to the histological studies of the placenta,
many researches have been made in the subject from earlier times, but a great majority of these researches were confined
to the development or general construction of the placenta,
and very few authors have given any special consideration to
the internal secretion of this organ nor have they closely examined the minute construction of the tissue elements or cells of the
 
placenta, Already Ahlfeld (’78) had noted the appearance of‘
-vacuoles in the syncytium layer, and subsequently many authors
 
recognized it; however, regarding the thing itself and its physiological significance, nothing definite has yet been stated. Gottschalk (’90) deemed it a pathological product; Kossrnan (’92)
took it for a kind of degeneration, while Langhans C92) interpreted it as ‘Leichenerscheinung. ’ Further, regarding the globules of fat in the same layer, demonstrations had already been
made by Pela-Leusden (’97) and Marschand (’98). Bonnet
(’99) deemed it a nutritious matter taken up by the embryo,
and in recent times authors have generally agreed in recognizing it as nutritious matter of the embryo taken from the mother’s
blood. Others, among them Halfbauer CO5), Costa C04 and
’O5), and Bondi (’11), inferred that the appearance of this matter
must be due to the active functions of the cells, by which it is
assimilated and absorbed. On the other hand, however, Wolff
(’13), as per Letulle and Larrier as mentioned above, on comparing the granular body of the syncytium layer with the secretory grains Within the ordinary gland—cells, stated that both of
them were a similar production. This theory was subsequently
supported by Fraenkel, who was close to the deduction that
there might be existent a certain secretory relation in the granular body of the syncytium layer. ,In short, the histological
studies of this subject up to now have been confined, as mentioned above, to the construction and, consequently, the functions
of the syncytium layer only, and there are even many defects
in the studies and some resultant weakness in the point of the
arguments, and no one can say that the opinions agree. Although there are some authors who recognized the internal secretory functions of the placenta, yet, sinceitheir arguments are
based on a single part of the organ, viz., the syncytium layer,
it must be stated that on the whole the basis of histological arguments for internal secretion in the placenta is very feeble
indeed, and much more is still to be done to accomplish a
consummate investigation of this subject. It should none the
less be added that Fraenkel (’14) was one of those who were
strongly opposed to the various theories given above, and he
denied the effects, which, it was believed, the placental functions have upon the mammary glands, on the ground that exactly the same phenomenon as takes place in the suckling of
mammals was observed in the suckling of Monotremata and
Marsupialia, neither of which has the placental formation. In
addition to that, Fraenkel, going so far as to discuss the‘ changes
which the internal secretory glands and other organs have to
undergo in consequence of the placental extract as was witnessed
in the experimentations of the afore-mentioned authors, concluded
that such changes were attributable to several ingredients, his
so-called ‘Gift,’ contained in the extract. According to
Fraenkel, who contradicted the theory which generally is in
favor of the existence of internal secretion in the placenta, the
internal secretory glands first respond to this ‘Gift,’ and, as a
result, the other physical changes follow. In short, it may be
said with regard to the existence of internal secretion in the
placenta that, in spite of the numerous researches made along
the lines of experimentation, biological chemistry, and histology,
as I have mentioned above, the Views expressed are so varied
that no conclusionhas been reached, and, therefore, regarding
the real situation of this subject, it is at present not yet an established theory. M
Many authors have given their attention to the existence of
an. internal secretory function in the decidua, and have tried to
demonstrate it, Starling (’06), Sfameni, Gentili (’13 and ’ 14),
Schottlander (’14), Aschheim (’15), Gentili and Binaghi (’17)
being among the number. Starling conducted experiments on
the rabbit to find the effects which the juice extracted from
the mucous membrane of the uterus While in pregnancy exerts
upon the mammary glands, and the result was of a negative
nature. Sfameni for many years past had held that in the
decidual cells -there should be existent an internal secretory function, the basis of his arguments being the striking resemblance
from the view—point of morphology, between the decidual cells and
those of the other internal secretory glands. In order to demonstrate this, Gentili, in the same laboratory as Sfameni, carried
out experiments by the use of ' the decidual juice on the dog,
the rabbit, and the frog, and it was found that, similar to the
luteal cells of the ovary, the decidual cells have a special action
upon both the circulatory and generative organs. Schottlander
also, by assuming that it may be possible for the secretion of
the glandular cells in the spongious layer of the decidua in the
first month of pregnancy perhaps to enter the mother’s blood
directly, recognized seemingly that the uterine glands at times
have the significance of an internal secretory gland. Aschheim,
in 1915, by discovering plenty of lipoid in the decidual cells,
imagined the existence of a special function in these cells. Lastly, Gentili and Binaghi, by conducting a Inicrochemical experiment on the various tissue elements which form the decidua of a
cow, demonstrated the existence of a kind of lipoid in the tissues,
as reflexive of the correlation which it seems they believed existing between a certain function, particularly an internal secretion
of the decidual cells, and the lipoid. On a close examination of
the result of researches made by these authors, it must be stated
that even in those whose view was in favor of an internal secretion
in the decidua the basis of arguments presented is in general as
feeble as in the case of an internal secretion of the placenta.
 
It is a long time since I began to feel interested in the secretory function of the placenta and the decidua. I was ever of
the opinion that both the placenta and the decidua have a
certain secretory function, and the experimental method I
adopted in investigating this subject was entirely different from
that employed by the foregoing authors. That is to say, I conducted a serological research into the effects which the alchoholic
extract of the placenta and the decidua has upon the mother’s
blood, and the result was the discovery in the serum during
pregnancy of, not only the well-known Abderhalden’s ‘Abbauferment,’ but also of such an antibody as has a property of
the fixation of complement- with ingredients of the extract referred to. And, as in ordinary cases, the'antigen which represents
the phenomenon of fixation of complement is either a proteid‘ or
some such like matter, whereas in my case it is a substance which
is soluble in alcohol, the latter must be deemed to be qualitatively
different from the former. It makes me feel as if it were in order
for me to presume that the antigens in my case are due to the lipoid
substances which are peculiar to (having some relation with the
secretory process of) both the placenta and the decidua. Accordingly I have become convinced that, in spite of the various authors
whose arguments I have enumerated above as denying the existence of an internal secretory function in both the organs concerned,
the fact must be the reverse. Needless to say, however, this
argument is only along lines of reasoning, and, therefore, it must
be stated that the reason why I have applied at this juncture
the modern cytological methods, thus planning out a close
histological investigation of the principal tissues and cells, particularly the cell bodies of the placenta and the decidua, was because
I was anxious to decide more clearly the right or wrong of this
hypothesis. I have also, by adopting the same methods, examined the minute structure of the principal cells as indicative of
the change which the uterine mucous membrane undergoes prior
to menstruation, which, being compared with that during pregnancy, has enabled me to arrive at a certain conclusion, as will
be noted later, respecting the physiological significance of the
menstrual changes of the uterine mucous membrane.
 
MATERIALS AND METHODS
 
The materials for research were taken from a total of fortythree cases, of which twenty-five had to undergo artificial
interruption during the first half of pregnancy because of the
following diseases: 6 cases of morning—sickness of high degree,
12 cases of phthisis, 2 cases of laryngeal tuberculosis, 1 case
each of consumption of the bowels, of peritoneal tuberculosis,
and of a valvular disease of the heart, 2 cases of glucosuria.
 
Of the remaining 18 cases, 14 had to undergo artificial interruption during the second half of pregnancy because of the following diseases: 1 case of beriberi, 5 cases of nephritis, 2 cases of a
valvular disease of the. heart, 1 case of albuminuric retinitis,
3 cases of eclampsia, 2 cases of placenta praevia.
 
And the remaining 4 cases had to receive a Porro’s operation
because of the following diseases: 1 case of mislaid transverse
position and 3 cases of the narrow pelvis.
 
And as to the time of pregnancy in these 43 cases, it should
be noted that 4 cases were less than 1 month, 2 cases 1 month,
4 cases 2 months, 7 cases 3 months, 6 cases _4 months, 3 cases
5 months, 4 cases 6 months, 3 cases 7 months, 3 cases 8 months,
 
4 cases 9 months, and 3 cases 10 months. And difiicult as it
was to accurately determine the exact time of pregnancy in each
case, the method I adopted in determining those less than one
month was to take into account the size of the egg and the degree of development of the embryo and villi, and in those one
month and upward, to consider the time of menstruation, the
size of the uterus, the length and weight of the embryo, the
length of the navel string, and the weight of the placenta, thus
arriving at the approximate time of pregnancy.
 
As regards the obtaining of the materials from the fetal placenta, it should be noted that in the early stage of pregnancy
a few pieces of ordinary villi from the surface of the ovum
were taken, while in a little more advanced a few small cuts of
the chorion frondosum, and in a well-formed stage of the placenta a few small bits of the latter have been cut out. Now,
as to the maternal part of the placenta, a part was taken
from placenta already delivered and from that not grown
up yet, in the former case, from the surface opposite the uterus
of the placenta, and in the latter, the mucous membrane of the
uterus concerned being scratched off quickly,ras during an operation it is quite easy for the operator to determine the insertion
of the placenta. The tissues obtained in this Way have always
shown“ microscopically, besides the proper decidual tissue, the
existence in them of parts of villi, syncytium cells, and the deposit of fibrinoid material (‘kanalisiertes Fibrin’ ofl Langhans),
all of which were proof that they were the materials I desired.
In this connection it must be added that the decidual materials were always taken from the decidua Vera only, at every stage of
pregnancy, by means of scratching out. All these pieces of tissues
were so taken that they should not exceed a cube 3 mm. in size,
and immediately after cutting they were dipped in the newly
prepared fixing solutions. For the latter I have ‘used: 1,
Altmann’s fluid of potassium bichromate and osmium tetroxide;
2, Flemming’s solution modified by Benda; 3, F1emming’s solution modified by Meves; 4, Levi’s mixture of formol, osmic acid,
potassium bichromate, and corosive sublimate; 5, Luna’s mixture
of formal, potassium bichromate, and glacial acetic acid. Each
of the pieces was then treated in the usual manner being imbedded
in parafiin and cut in sections of 3 to 4 pt. And as a treatment prior
to staining, Rubaschkin’s method has been applied in a great
majority of cases. For staining I have employed: 1, Altmann’s
method of acid fuchsin and picric acid; 2, Heidenhain’s iron-alumhaematoxylin, and, 3, Benda’s alizarin—crystal-violet method,
etc. All the methods which I have adopted, the fixation with
Levi’s mixture, and the staining with iron—alum-haematoxylin
have been found to be comparatively successful.
 
MY OWN OBSERVATIONS
 
The chorionic villi, which are a, main component of the placenta’
consist of: 1) the syncytium cell-layer; 2) the Langhans’ cells’
and, 3) the ‘Stromazellen,’ being cells in the stroma of villi»
while the components of the decidua serotina and the decidua
Vera chiefly consist of, 4) the decidual cells and, 5) the epithelium of the uterine gland. In the present chapter I intend to
give a detailed account, mainly from the histological standpoint,
of these important tissue components, or cell groups, especially
as they appear in the different stages of pregnancy. However,
since the structure of all kinds of cells varies even in the same
stage of pregnancy and in the same group of cells, it would be a
difficult task indeed to explain clearly the correlations existing
between the minute structural changes of these cells, or cellular
groups, and their functional significance. Therefore, I have selected and drawn those deemed the most representative of all
the structural images of the afore-mentioned tissue-cells which
have been widely and thoroughly examined, as will be seen from
the series of figures on the plates the object being to give a general
idea of the structural changes of these cells. The explanations
of each of these figures will make the pith of this chapter, as by so
doing I believe the description could be much simplified and its
understanding facilitated as much as possible. Thus, I " shall appreciate very much if the reader will constantly refer to those
figures While reading.
 
(1). The syncytium cell-layer (figs. 1 to 12)
 
As is well known, the syncytium layer is the epithelium which
covers the surface of the villi, and the lack of boundaries between
the cells is a feature of this layer. And it is also well known that
within this layer there are several kinds of nuclei, differing in
size and form and scattered here and there, besides dark-colored
granular bodies and a great number of vacuoles which occasionally appeared in it. Its surface is covered with a brush—like
border. This layer is generally well developed in the early stages
of pregnancy, but in the second half of pregnancy it becomes
thinner and looks much like an endothelium, so that, when examining its minute structure, it will be necessary to do so before the
fourth month of pregnancy. Figure 1 shows that part of the
anchoring villi which extends deeply into the decidua, while all
the other plates show the different parts of the surface of the
ordinary villi.
 
In figure_ 1 the syncytium presents a homogeneous protoplasmic layer generally dark-colored and contains an extremely
large quantity of plastosomes (mitochondria). They are of
different shapes, but mostly are rod-shaped or bacteroid and of
different lengths, the longer ones being slightly curved. They
arrange themselves in groups rather than being equally distributed over the layer, and in some places some of them point in
the same direction, while others point in Various directions, thus in general‘ giving ‘them something of a meshy arrangement.
The nuclei are clear and have in themselves a more or less conspicuous nuclear network, with one or two nucleoli.
 
In figure 2 the syncytium layer closely resembles figure 1 in
structure, though the plastosomes contained therein differ from
one another in their shape, arrangement, and number. These
two figures show the simplest structure of the syncytium layer.
 
In figure 3 the plastosomes are generally faint and quite
scattered; in the protoplasm there are some dark-colored granular bodies of different sizes and a small number of vacuoles;
the smaller granules are somewhat dark in color and are generally found very near the surface, viz., the brush-like border,
whereas the larger ones are light-colored and are found in other
parts of the layer. The vacuoles are found close to the Langhans’ layer. The nuclei are irregular in shape, and besides the
nuclear network there are one or two nuceoli.
 
In figure 4 the plastosomes are generally found in the
deeper layer, i.e., close to the Langhans’ layer, and they are
comparatively small in number. On’ the contrary, however,
plenty of dark or yellowish dark—colored granules occur
conspicuously all over the layer, the deeper colored ones being
generally superficial. Undoubtedly, granular bodies of this
kind have grown up from the dark-colored granules in a conspicuous manner such as I have shown in figure 3 above, and
they are very frequently met with elsewhere in the other parts
of the syncytium layer. And, moreover, granular bodies of
a similar kind are found, as will be seen in the following statement, not only in the syncytium layer, but also commonly in
other cell groups. These granular bodies are, of course, extremely varied in their size, quantity, and color; however, .since
they have a common aflinity to certain chemical and coloring
matter, e.g. osmic acid, iron-alum-haernatoxylin, and acid fuchsin, etc., I have followed, for the sake of brevity, the precedents
of many histologists in including all these granular bodies under
the name of ‘lipoid’ granules. In this figure there is, moreover,
only one vacuole close to the brush-like border. The nuclei are
less conspicuous in their network, the chromatin forming itself into a large number of lumps, each of nearly equal size.
 
In figure 5 there are no plastosomes to be found, but the lipoid
granules occur in extremely large quantities, and their sizes
are nearly the same. They are found more or less in groups
and are distributed all over the layer. At the same time the
vacuoles make their appearance in a conspicuous manner, sometimes on the surface, sometimes in the innermost part, and sometimes in the middle, and they are about the same size as the lipoid granules. As is well known, it is in general very difficult
to stain the plastosomes every time, and, therefore, accurately
to determine their existence and where they are entirely wanting, as in this figure, it would be a very difficult task indeed.
I have paid the closest attention to this, and have always
selected for it the most excellent preparations for staining,
with a View of doing away with all the possible defects in the
technique of staining. From the existence, in a very conspicuous manner, of plastosomes in the neighboring tissues, entirely
in contrast to this figure, I was prompted to conclude that it
was well nigh necessary for me to assert the absolute lack of
plastosomes in this part of the syncytium layer. Further, I
may add that, as will be noted below, the same amount of attention has been given all the other cells where there are no plastosomes to be found, and I, on this score, am convinced that my
observations concerning them are not erroneous.
 
In figure 6, the surface is somewhat light-colored and is clear.
In it there are found innumerable quantities of vacuoles which
are nearly of the same size, besides a small number of Iipoid
granules. The innermost part, however, is of a comparatively
dark color, and it likewise contains innumerable quantities
of minor lipoid granules of about the same size, with very few
vacuoles which are generally of small size. Some of the nuclei
are oval, while others are irregular in their shape, and there
is to be found a great number of chromatin granules which
make their appearance in lumps of different sizes; the nuclear
networks are usually less conspicuous. There are absolutely
no plastosomes to be found.
 
 
In figure 7 the syncytium layer is extremely thick, and it is
difficult to demonstrate the plastosomes. Lipoid granules of
extremely varied sizes are found in large quantities. These
granules are irregularly arranged, and they tend more or less
to occur in groups; certain lipoid granules make their appearance as contents of vacuoles, in which case the granules always
have a clear halo around them, as if they constituted the nucleus
of the vacuoles. Such images are frequently met with not only
in the syncytium layer, but also in other cell groups and, since
theylare worth recognizing as very clearly indicating the relations
which exist between the lipoid granules and the formation of
vacuoles, the reader’s special attention is hereby drawn to this
point (vide the left-hand side of this figure). The vacuoles are
abundant, and their sizes and shapes are quite irregular and, as
will be seen in the middle part of this figure, a great number
of them are joined together at some places without boundaries
being noticeable between them. From the existence of such
images I am led to infer that an extraordinarily large vacuole
is in general the outcome of minor vacuoles being agglutinated
and joined to one another. In this Way, it seems that the
vacuoles which have grown up into tremendous sizes finally
rupture toward the surface, as it will be seen in the present
figure that such vacuoles open up and connect directly with the
intervillous spaces, clearly supporting the interpretation that I
 
have given above.
In figure 8, it is in general extremely deficient in its character
istic dark-colored protoplasm, but then there are all over the
layer numberless vacuoles of a very small size, which grow so
close to one another that they have exactly the appearance of
a beehive. Of these vacuoles some of the larger ones lie together close to the surface, while others, connected with one
another,. mutually find their outlets to the surface through
comparatively large openings. Because of these openings the
surface of the syncytium layer, which is naturally level, becomes
very uneven and irregular. The lipoid granules are very few,
and no plastosomes are to be found. The nuclei are not only few, but being shrunken are changed into homogeneous bodies
of small size, the nucleoli alone making a prominent appearance
(vide the right-hand side of the figure).
 
In figure 9 the syncytium layer is comparatively thin,
and there are comparatively few plastosomes to be found, being
scattered here and there, and mostly rod-shaped. The lipoid
granules'are middle-sized and are not many in number, and a
few of them stay at the center of the vacuoles as if they were the
nuclei of the vacuoles. The vacuoles are pretty large, and they
arrange themselves close to the Langhans’ cells. The nuclei
have distinct borders and masses of chromatin arrange themselves in rows, usually close to the nuclear membrane.
 
In figure 10 the protoplasm is, as in a majority of cases,
generally dark-colored, though not homogeneous altogether and,
on a close examination, it is found that it contains a great number
of vacuoles, which gives the protoplasm more or less a foamy
appearance, though very indistinct as compared with other
foamy structures. The plastosomes are mostly rod—shaped and
are very distinctly stained. They appear generally in the upper
layer, though some are noticeable in the innermost layer. There
are no lipoid granules to be found and no nuclei of normal conditions are to be met with, but, on the contrary, there are some
curious bodies, whose size is somewhat larger than the ordinary nuclei and which are irregular in shape. Some of them
are homogeneous and are quite dark-colored, while others being
non-homogeneous consist of different parts which are either
dark or light or somewhat clear when stained. We come
across such structures very often_in other parts of the syncytium
layer, but so far I have not been able to find out their original
nature.
 
In figure 11 the protoplasm shows numberless vacuoles as its
constituents. The vacuoles are somewhat varied in their size,
and with the exception of some which are full and stained, a
greater portion of them, particularly those which are found on
the surface, are more or less loose and somewhat flattened in
shape. Between these vacuoles there are extremely large
quantities of plastosomes, which are mostly rod— or granula  shaped and equally deep—colored as these which are found in
figure 10. There are few lipoid granules to be found, and they
exist for the most part in the superficial layer, scattered here
and there. What is especially worth noting is that there are red
blood corpuscles in the protoplasm between these vacuoles (vide
the left—hand side of the figure). The nuclei are oval-shaped,
and the chromatin is very peculiarly arranged, its outward
appearance resembling the shape of a chrysanthemum. In the
center there is a nucleolus, and it must be noted that a nuclear
condition of this kind is generally very rare.
 
In figure 12 the protoplasm is glutted with numberless vacuoles, andit is for this reason remarkably foamy in appearance.
The vacuoles are of two sizes, of which the smaller ones are
mostly located in the deeper portion and make a somewhat
continuous layer, though in other parts there are to be found
some of these smaller-sized vacuoles also. The larger vacuoles
are crowded together in the middle part of the layer, and some
of them burst forth onto the surface, While others make their
appearance in the innermost layer close to the Langhans’ cells.
The plastosomes are quite uniform in shape with those illustrated in the preceding figure, and they are all found in the protoplasm between the vacuoles. The lipoid granules are nearly
of the same size and are found at several places, some of them
with the halos distinctly described. The nuclei appear to be
somewhat smaller in size, but there are no remarkable change
in their structure. . .
These structural conditions in the syncytium layer which I
have illustrated and described ‘above can be detected at almost
any time and place at the different periods from the first month
of pregnancy to nearly the fourth, and, therefore, there is no doubt
that these structural changes cannot be taken as a measure to
tell the precise time of pregnancy. At no time after the fourth
month of pregnancy can we detect the plastosomes. The lipoid
granules and vacuoles reach their maximum growth from the
second to third month of pregnancy, and after the fourth month
they gradually begin to decrease, entirely disappearing after
the seventh month. The syncytium layer comes in sight  a remarkable manner on the seventeenth or eighteenth day after
pregnancy, reaches the maximum of growth at the end of the
first month, and from the second to the third month it seems,
although not very conspicuously, more or less reduced in thickness, but after the fourth month it suddenly becomes thinner,
and simultaneously its structure becomes simplified, and in the
seventh month it will altogether atrophy and remain simply in
the form of a thin membrane like an endothelium. Moreover,
in the last two months the layer will disappear in some places
and will be noticeable only as a discontinuous thin cover. In
other words, this layer, excepting in the early stage of pregnancy,
always decays and goes out of existence in inverse proportion
to the growth of the embryo, and this is the very point which
should engage the careful consideration of those who are interested in the functions of this layer.
 
2. The Langhans’ cells (figs. 13 to 26)
 
The Langhans’ cells have in general distinctly clear bodies,
and are distinctly bordered with a thin membrane (pericula?) on
the surface. Their sizes, shapes, and structures are extremely
varied; on examination of the smallest cells (figs. 13 to 16 and
7, 8 and 10) it will be found that they are either round like a
ball or oval-shaped, with foamy nuclei of corresponding shapes
inside. The structures of the cell bodies consist of quite structureless stroma and a large quantity of plastosomes, of which the
latter are rod-shaped in several lengths, and are usually distributed all over the cells, though sometimes they crowd together
on one side of the cells. There is occasionally a small ovalshaped body somewhat dark in color close to one side of
the nucleus, which might possibly belong to Meves’ so-called
‘Centrotheca;’ it, however, lacks a centriole within (fig. 13).
Within the nuclei there are generally one or two conspicuous
nucleoli, and in most of the cases it is difficult _to discern the
nuclear network. In the large sized cell bodies (figs. 17 to 19
and 2, 3, 9, 11 and 12) we always find either a small quantity
of lipoid granules or vacuoles. The lipoid granules are nearly
the same in size, and, though small in number, they are scattered everywhere (figs. 17 and 11). The vacuoles are extremely varied in their size, quantity, and arrangement, and it is for this
reason that the structures of the cell bodies have so many special
features (figs. 18, 2, 3, and9). In such vacuolar cells the rod-shaped
plastosomes are for the most part short in length, and they are
arranged either along the walls of the vacuoles or crowded together
in the protoplasm between the vacuoles; however, sometimes it
will be found that, as will be seen in figure 18, the vacuoles are
chiefly placed in order on the outskirts of the cells, and the
plastosomes accumulate in the center around the nucleus. Again,
it will be found that, as in figures 19 and 12, both the lipoid
granules and vacuoles of various sizes are simultaneously contained in the cellbodies, in which case the plastosomes are comparatively small in number and are scattered here and there
in the protoplasm between the lipoid granules and vacuoles.
 
In the largest cells (figs. 20 and 21) the cell bodies are in general well filled with a great number of vacuoles of various sizes,
and consequently the protoplasm is noticeable only around the
nucleus and between the vacuoles. There are almost no lipoid
granules, which, when present, are small and are very few in
number; also the plastosomes decrease in quantity and are mostly
found around the nucleus.
 
In short, the smaller-sized cells have in general only the
plastosomes as their material components, while the largersized ones still contain a number of lipoid granules and vacuoles
and in the largest ones the cell bodies are commonly vacuolated
in a high degree and the protoplasm decreases considerably in
quantity, the plastosomes in general gradually decreasing in
number as the cells grow in size, though -it sometimes happens
that it is very difficult to demonstrate them, regardless of the
size of the cell bodies. Of figures 22 to 26 it will be observed
that figure 22 shows the lipoid granules only, figure 23 chiefly the
small vacuoles and a few lipoid granules; in figure 24 it is
entirely the same as the former, however, with the distinctive
feature that the vacuoles are remarkably large and have lipoid granules of various sizes within; in figure 25 and 26 the
bodies are vacuolated to the highest degree, and it is perfectly
plain that the vacuoles which are extremely varied in size and
shape mix together and grow larger, thus giving the cell
bodies the appearance of a honey comb in a striking manner. The
large and highly vacuolated cells such as are-illustrated in figures
21, 25, and 26 are very frequently met with in the Langhans’
islets.
 
The various structural images in the Langhans’ cells that I
have_ described above make their appearance in a most remarkable manner from the end of the first month of pregnancy to
the end of the third month ,and in the fourth month, though
the plastosomes are still existent in a remarkable degree, the
lipoid granules and vacuolar formations are no linger conspicuous, and in the‘ following months not only do the cells decrease
suddenly, but also these materials component of the cell bodies
disappear, though the cells in the Langhans’ islets retain those
structures as long as they exist.
 
3. The stroma cells of villi (figs. 27 to 38)
 
The smallest of the stroma cells of villi, as is illustrated by
figure 27, are mostly ball—shaped and have the nucleus of a
similar shape within. In the cell bodies there are plastosomes,
mostly rod-shaped. Figures 28 and 29 are nearly the same
as figure 27 in their shape, though the one contains in the cell
body a somewhat large quantity of lipoid granules of different
sizes, while the other has a small quantity of extremely small
lipoid granules and an equally small quantity of small vacuoles.
Figures 30 to 38 illustrate the cells arranged in their approximate
order of size and, though their shape and structure appear extremely varied at a glance, it will be ‘found on close examination
that, with the exception of figure 34, there is a structure which is
common to nearly all the rest, the only difference between them being principally the size and number of vacuoles contained in
the cell bodies. Generally speaking, the larger sized-cells have
vacuoles which are naturally large in size and number, and the fact that large vacuoles are built up to some extent from the fusion of the smaller vacuoles which are connected with
one another can be often proved in these stroma cells (fig. 38).
The plastosomes are mostly rod-shaped and lie scattered in the
protoplasm located between the vacuoles, though they sometimes crowd together in a somewhat larger number in certain
places (figs. 31, 32, 36, and 38). The lipoid granules are generally few in number and are found between the vacuoles, though at
times they are present‘ within the small vacuoles (fig. 36).
The smallest of these lipoid granules, at a glance, bears a close
resemblance to the granular plastosomes; however, since they
are mostly very distinctly bordered, besides being stained darker,
it is easy to distinguish them from the former (figs. 36, 37,
and 31). Figure 34 looks somewhat different from the various cells described above in that the cell is nearly spherical,
with a remarkably large nucleus within, besides a small number
of somewhat large vacuoles and plenty of lipoid granules in
the cell body. These granules have Various sizes, but are in
general of middle size and a few of them are distinctly included
in the vacuoles. The plastosomes are extremely limited in number, and lie scattered in the protoplasm between the vacuoles.
It is very seldom that this kind of cells makes its appearance,
and a great majority of cells in the stroma, as are chiefly illustrated by figures 35 to 38, present a distinct vacuolar formation.
 
The plastosomes in the stroma cells have in general a very
strong staining power, and are therefore more easily detected
than other cell groups. It is, moreover, very rare that the cells
which have no plastosomes are met with, but in stroma cells the
lipoid granules seldom appear. The stroma cells appear distinctly
and are therefore most easily found during the period from the
second to sixth or seventh month of pregnancy. In the eighth
month, usually, numberless capillary blood vessels suddenly grow
and increase within the villi, so that it is impossible to examine
the cells. With every possible method it was difficult to detect
the cells, and, therefore, I am inclined to believe that the stroma
cells suddenly cease to exist at this stage of pregnancy.
 
 
4. The decidual cells (figs. 39 to '71)
 
It is a generally well-known fact that decidual cells are divided
into very many kinds according to shape, size, staining properties, and structure; however, it has not as yet been definitely
decided whether or not these kinds of cells should be reckoned
as one and the same sort. Marschand (’04) first divided the
decidual cells into two types according to the difference in size.
Subsequently, Fraenkel (’14), too, who studied them chiefly
from the staining standpoint, set up a similar theory, and tried
to divide them into his so-called acid cells (Eckersche Form)
and the neutral cells (of large type); however, he himself and
others had no doubt that there was not only no distinct division between these two kinds of cells, but rather there was existent an intermediate type of cells between them.
 
Figures 39 to 69 illustrate the Various kinds of decidual cells
placed in order. Of these, cells such as in figure 39 are the smallest
and are spherical with a nucleus of a corresponding form. The protoplasm is, as compared with the interstitial cells at the time
of non-pregnancy, remarkably large in quantity, and contains
in it a' large number of rod-shaped plastosomes. Figures 40
and 41 are a little bit larger than the former, and the one is
spherical while the other is oval, both having a nucleus of
nearly corresponding shapes. The protoplasm becomes still
more abundant and the plastosomes are somewhat longer
rods. It is worth our noting that both cells have a kind of
boraer membrane already on the superficial layer of the cell
bodies. Figure 42 demonstrates the first appearance of a few
lipoid granules of various sizes within the cell bodies. Figure
43 illustrates a pear-shaped cell, which holds in the body a somewhat large quantity of granules and a few vacuoles. A few
plastosomes are to be found, and they make their appearance
only on one side of the cell. Figure 44 resembles the former
in shape somewhat, and contains in the cell body remarkably
large lipoid granules, which, on a close examination, are found to
have a more or less distinctly clear halo around each of them, as
though they constituted the contents of vacuoles. The plastosomes are mostly rod-shaped, and they crowd together on
one side of the nucleus, while on the other they appear in a remarkably long, granular string (Fadenkorner). In figures 45 to
48 the cells have exceedingly Varied shapes, and the nucleus
trends toward one side of the cell close to its superficial layer.
The cell bodies are filled with numerous irregular-sized vacuoles,
which present a more or less distinct foamy structure. The
plastosomcs are mostly short and rod-shaped and they are to be
found in the proplotasm between the vacuoles. Some of them
are arranged in a long row along the walls of the vacuoles, While
others are found in groups in a certain section. The lipoid granules are, in general, small in number, and their sizes are irregular, some of them finding themselves distinctly at the center of
the vacuoles (e.g., fig. 46). '
 
In the various cells described above it will be observed that
the nuclei are generally dark—colored, with indistinct nuclear
network in most of the cases, though the nucleoli contained are
conspicuous enough. Figure 49 is extremely different in its
appearance from these cells. The cell body presents a vacuolar
formation in high degree and the protoplasm proper can be
demonstrated in a small amount only along the surface of the
nucleus, at which place only a few rod-shaped plastosomes are
found. The border membrane on the surface of the cell is very
distinct and the nucleus is different from that in the various cells
described previously in that it is clear and presents a large foamy
body. The nuclear network is somewhat distinct, and, besides,
there are conspicuous nucleoli. It must be generally stated that
this kind of cell appears very seldom. In figure 50 the cell body
presents an equally high vacuolar formation as in the former, and,
in addition to that, the vacuolar walls entirely disappear in some
places and so allow the inner spaces of the vacuoles to communicate with one another, thus clearly indicating the evidence
of the vacuoles having been agglutinated. A few more plastosomes than in the former are found in groups in these cells, and,
besides, there is a small quantity of lipoid granules, mostly
within the vacuoles. What is especially peculiar about this
cell is that at the center of the cell body there appears a black colored homogeneous star-shaped lump, from the surface of
which are shot forth a number of processes, which run over
directly to the protoplasm between the vacuoles. The proper
nucleus is hardly detected. In figure 51 the cell is longish,
and the overabundance of plastosomes which are distributed
densely almost all over the cell body is the feature of this cell.
Between there, is a somewhat large number of vacuoles of
various sizes, and no lipoid granules at all are to ‘be found.
 
In figures 52 to 54 thevarious cells illustrated are gradually
larger than those described above, the cell bodies are filled with
a large number of vacuoles and granules. The latter are extremely irregular in size and density and are sometimes found as
contents of the former. The plastosomes are mostly short rods,
and especially in figure 52 they are somewhat abundant, and
some are found massed along one side of the nucleus. In figures
53 and 54 they are comparatively fewer and lie scattered between
the vacuoles. The thin layer on the surface of the cell is
thicker and more distinct in this kind of cell, to such an extent
that it almost reminds us of the ordinary cell membrane. In
figure 53, as in figure 50, we notice a black—colored round—shaped
lump at the location of the nucleus; however, in this case, the
surface of the lump is smooth and has no process. Comparatively
few cells have such a black—colored lump, and, as in these
cells it is always difficult to tell the whereabouts of a nucleus
of normal condition, I am quite at a loss to know whether or
not the dark lump described above should be deemed a modification of the nucleus or regarded as that part of the protoplasm
which is just adjacent to the nucleus which has, by reason of
its staining properties, obscured the nucleus. This question,
along with the stained lumps in the syncytium layer as illustrated
in figure 10, constitutes a puzzle, and I have mentioned it here
for the sake of future investigations. However, in View of the fact
that numerous plastosomes, which are the important elements of
a living cell, are always demonstrated in the cells concerned, while
at the same time they present no noticeable regressive phenomena.
I am rather inclined to believe that it is possible to attribute a
certain functional significance to these unknown lumps.
 
 
The cells illustrated in figures 55 to 57 are already exceedingly
large, and they are, at a glance, recognized as Marschand’s
so—called large-type of decidual cells. On the surface there
is a rather thick layer, which may be divided into two of which
the inner one is thick and the outer thin, and they exactly
remind us of the definite cell membrane. The cell bodies consist
of plastosomes, lipoid granules, and structureless stroma. The
plastosomes are mostly long rods or threads, some being more or
less peculiarly curved and the quantity of plastosomes is variable.
The lipoids differ also in point of size, density, quantity,
etc. What is worth our noting is that there is no vacuolar
formation to be found in these cells. The nuclei are large, clear,
and foamy. The nuclear network is especially conspicuous in
figures 56 and 57. Figures 58 to 61 show the definite form
commonly belonging to the- so-called decidual cells of large type.
In these cells the cell membrane is remarkably thick, and the
distinction between the inner and outer layers is always clear.’
What deserves our special attention at this juncture is that the
outer layer contains, in most cases, ‘a kind of granular body
which is somewhat large and yet irregular in sizeland stained
a dark color. The cell bodies consist of a large quantity of
plastosomes and homogeneous stroma. The plastosomes are
mostly long rods, and they sometimes appear extremely elongated
in the shape of threads (fig. 61). They are distributed equally
all over the cell bodies, although they sometimes tend to appear
more or less in groups. The plastosomes in these large cells
have, in general, very slow staining properties, and, therefore,
they are a very difficult subject to be dealt with from the technical point of view. The nuclei are foamy and dark—colored,
and the nuclear networks are indistinct.
 
The cells illustrated in figures 62 to 69 differ from those described above, and they all lack the plastosomes. Even in the
most excellent stained preparations these cells appear within
the decidual tissues in small numbers, for the most part more
or less in groups, scattered like islets, so that it is, as a matter
of course, incomprehensible that here alone the plastosomes
are hard to be demonstrated. However, as, in consideration of their structure and shape, it is premature yet to decide posi
tively that there is a tendency for a retrogressive change,
 
among all these cells, I will here suggest provisionally that such
a phenomenon is a sign of a certain functional period in the
cells concerned. Now, at first, in figures 62 and 63 the cell
bodies are comparatively dark, and within they contain a large
quantity of vacuoles and lipoid granules of various colors; some
of the vacuoles distinctly have a lipoid granule as their nucleus,
while others, being placed in rows close to thecell membrane,
present a peculiar image. The nuclei are clear and have a
somewhat distinct nuclear network. In figure 64 the cell body
is filled with numberless vacuoles of nearly the same size, and on
one side of the nucleus accumulates a large quantity of protoplasm, and, besides, there are a few deep yellowish-brown
lipoid granules. Figure 65 is of nearly the same type as the
former, but the lipoid granules contained are by far greater in
quantity than the vacuoles. The nucleus is as clear as the former, with conspicuous nuclear network. Figures 66 and 67
illustrate the cells whose bodies are filled with an exceedingly
large quantity of vacuoles of various sizes, in consequence of
which the protoplasm becomes comparatively scarce and faint
and is mostly noticeable only around the nucleus. And, besides,
there are some vacuoles which hold dark or deep yellowish-brown
lipoid granules; also vacuoles and lipoids, Whose size, quantity,
and distribution are as varied as will be seen illustrated in the
respective figures. The nuclei are generally dark and show
extremely delicate network formations.
 
Figures 42 to 48 and 51 may be compared, from their sizes and
histological point of View, with that class of cells which is termed
by many authors as ‘decidual cells of small type’ (or possibly
Ecker’s type), While, on the contrary, figures 55 to 61 and 64
to 69 may be nothing but the so called ‘large-type’ or ordinary decidual cells (neutral cells). Further, the various cells
illustrated by figures 49, 50, 52, 53, 54, 62, and 63, judged
from their size and internal structure, should be deemed an intermediate type which may intervene between the former two,
since it is a very diflicult task to determine to which one it should belong. Now, the result of my careful examination of
the appearance and distribution of these cells as compared with
the time of pregnancy has been that, in the material which was
taken a fortnight after conception, this being the earliest I have
on hand, the cellular ingredients of the decidua chiefly consist
of the small-type cells described above. In a little more advanced
stage (i.e., about 17 or 18 days after pregnancy) the decidua
shows also the appearance of a large quantity of the ‘intermediate-type cells,’ while in the few days following (i.e., about 22
or 23 days after pregnancy) with the decidua already of definite
growth, all kinds of cells, especially the large-type ones, can be
detected in comparatively large quantities. One month after
pregnancy the large and intermediate type cells appear as the
principal ingredients of the decidua, while on the contrary the
small-type cells retrograde gradually and are met with only in
the interstitial tissue. Such condition is maintained until the
end of. the last month of pregnancy. In short, I concludefrom
the histological and histogenetical point of view, that the various
kinds of cells described above all belong to one class, and consequently it follows that the division of decidual cells into large
and small types, is faulty. In other words, the term ‘small-type
decidual cells’ applies only to the cells which are still at the
early stage of growth, while the ‘large~type cells’ are those'in
the last stage of growth. The time taken in -such growth is,
according to my observations at the earliest stage of ‘ pregnancy
at least, comparatively small, thus the small-type cells being
perfected into the ‘definite large-type cells’ in so short a time.
 
The appearance of lipoid. granules and vacuoles in the decidual cells is most remarkable from the end of first month to the
second month of pregnancy, and they gradually decrease in the
months following, though very infrequently they can be demonstrated even at the end of pregnancy. The plastosomes could
no longer be demonstrated in any of the decidual cells after the
seventh month of pregnancy. ' ' '
 
And, in the interstitium of the decidua, such extremely strangelooking productions as are illustrated by figure 70 may some
times be detected. They are stained dark and consist mostly of a great number of granular bodies which are extremely
varied in size. There are_ granular threads, which are the result
of the granules being linked together, more or less curved
large rod-shaped bodies of "different lengths, and sometimes
threads which are very long and often curved like screws, besides a large number of material ingredients, which, being
mixed up among them, have shapes similar to them and yet are
unstained and noticeable only as a shadow. The former, which
are susceptible to staining, are dyed deep red by Altmann’s
method and deep black by iron-alum-haematoxylin. At a glance
they look like plastosomes in their shape and staining, and yet
in general excel the latter in size considerably. If aggregated,
they may be quite easily detectedunder medium magnification. Moreover, the staining properties of the ingredients are
much stronger than the plastosomes, and they bear a rather
close resemblance to lipoids in their density and appearance.
The product of this kind do not only possess exactly the same
properties in shape and stain as the granular bodies in the cell
membrane of large-type decidual cells to which I alluded above,
but also indicate that there is often the closest relation between
the two; i.e., within the cell membrane of the cells concerned
there are, besides the granular bodies above referred to, often
short granular threads or large rod-shaped bodies, both of which
are similar to the substances in the interstitium described above.
One end of the rod-shaped bodies sometimes enters deep into the
cell membrane and swells into a club—like shape, while a greater
part -of the other end juts out into the interstitium, thus giving
itself the appearance of passing into the interstitial product.
I am not able to explain the original nature and functional
significance of this kind of product, and yet, according to the
afore-mentioned observations, I have no doubt Whatever that in
the formation of the product the large cell, and especially its cell
membrane, plays an important part and, since such interstitial
substances are "demonstrated in large quantities in the adjacent
blood vessels as are illustrated by. figure 71, it may be inferred
that they are ultimately absorbed in the vascular organs. The
products of this kind are for the first time noticed at about the second month of pregnancy, appear most conspicuously from the
end of the second month to the third, decreasing gradually after
that, and, though the decrease is considerable after the fifth
month, they may yet be demonstrated until about the sixth
month. Besides the above, there are detected in certain parts of
the interstitium numberless filar productions which have various
length, and are sometimes long like threads or fibers, of which
the smaller and shorter ones sometimes bear a close resemblance
to the plastosomes, while the others usually gather in great number and often make a mass of fibrous bundles. This kind of
product, so far as staining is concerned, is entirely similar to
the interstitial productions described above, and yet it differs
from the latter in that its shape is not so varied, its thickness is
nearly always even, and, besides there is no special relation which is noticeable as existing between the products and
neighboring cells.
 
5. The epithelium of the uterine gland (figs. 72 to 83)
 
As is generally well known, the uterine gland undergoes a certain morphological change at the early stage of pregnancy, and
in my previous treatise I have drawn attention especially to
the fact that the glandular cells also show a morphological
change at such a time. Here I will observe and describe more
thoroughly the changes of the cells concerned.
 
Figure 72 shows -a glandular cell which is commonly noticed
at the early stage of pregnancy and which is already remarkably
thickened and somewhat round. The shape of the nucleus for the
most part corresponds to that of the cell. On top of the cell there
are traces of cilia. The cell -body contains many slender
and rod-shaped plastosomes, which latter chiefly gather closely
against and surround the nucleus. In figures 73 and 74 the
cell grows larger, and the plastosomes are demonstrated only
in the upper half, while in the lower half which contains the
nucleus, none of them are found. At this section of the cell
there are plenty of lipoid granules, which are of about equal
size and are stained a bright yellowish-brown color, and on
top of both cells there are still the traces of the cilia. In figure 75 the cell is remarkably elongated, and within are contained
a great number of lipoid granules. The nucleus is oval with
a nuclear network distinctly observed; from this period on no
more traces of cilia are to be found. The various cells illustrated by figures 76 to 78 gradually increase in their size and,
since their swelling is remarkable, especially in the upper half,
it is usual that this partsof the cell naturally juts far out into
the lumen, though‘ the lower half, being comparatively narrow,
is closely united with the basement membrane. Within the
cell body are contained a great number of both lipoid granules
and vacuoles, of which the vacuoles in figure 76 are as yet
small and few and they chiefly occupy positions in the upper
half of the cell body, whereas in figures 77 and 78 the vacuoles
enlarge tremendously and fully occupy the upper half, in consequence of which cell bodies have the appearance of a honey comb
in a high degree, and the protoplasm remains only as a thin
wall which separates the vacuoles. The lipoid granules in the
latter two kinds of cells chiefly crowd together at the base of
the cell bodies, and only a small portion of them are left behind
as contents of the vacuoles. The afore-mentioned three cells
each present conspicuous nuclear network and nucleoli. And
in the various cells in figures 75 to 78 no plastosomes are to -be
detected.
 
Figure 79 illustrates a large oval-shaped cell, Which has a
similar-shaped large alveolar nucleus. The cell body, because
of the vacuolar formations of various sizes, presents the image
of a conspicuous honey comb, while the plastosomes lie scattered
somewhat plentifully in the interstice between the vacuoles.
Though there are some extremely small vacuoles in jet black,
no ordinary lipoid granules in coarse grains are to be found.
The contents of the nucleus are nearly homogeneous, and
the characteristic nuclear network is not found,’ but within
the nucleus there are two nucleoli. Figure 80 is an extremely
irregular-shaped cell, with the nucleus of a corresponding
shape. The structure of the._cell body is nearly the same as
that in the preceding figure, and the vacuoles are somewhat
plentiful, but the plastosomes are very few, and, besides, there are but few yellowish lipoid granules. The nucleus has a conspicuous network. .
 
As the change of the glandular cells reaches a high degree,
the cells leave the basement membrane in large numbers and
are isolated in the glandular lumen. Such cells I call temporarily the ‘desquamated cells’ in contrast to the cells which
continue to settle on the basement membrane or remain
fixed on the walls. Figures 81 to 83 illustrate my so-called
desquamated cells, in the inside of whose cell bodies there are
many vacuoles and a small number of extremely small lipoid
granules which are stained in black. At a glance they look
like the ‘wall-fixed’ cells, and yet on a careful comparison we
find that there is a more or less remarkable difference between
them. That is to say, in the desquamated cells the cell bodies
are in general somewhat turbid, and also the vacuoles look
somewhat withered and decayed. No plastosomes are to be
found, and, besides, the change of the nucleus is remarkable,
as will be seen in figure 81. Here it is converted into a darkcolored and homogeneous lump provided with a Very irregular
contour, having within a few small nucleole-like bodies. In
figure 82, as before, the nucleus is simply a homogeneous and
dark-colored lump; in figure 83 it has swollen somewhat remarkably, and the nuclear network‘ is extraordinarily conspicuous. In short, the desquamated cells hav_e undoubtedly began
a retrogressive degeneration already, andfrom the existence of
many broken pieces of cells which are always found in the glandular lumen it can be simultaneously demonstrated that the desquamated cells are doomed to break up and perish at this section sooner or later. The various changes undergone by the
glandular cells described above are seen in a remarkable degree already on about the seventeenth or eighteenth day of pregnancy
in the decidua serotina, while in the decidua vera it is a little bit
later and the changes are noticed to about the same degree as the
former only toward the end of the first month of pregnancy. Both
reach the maximal changes at about the end of the first month of
of pregnancy, and on the days following they gradually pass into
the so-called desquamated cells and break up and perish as such.
 
 
The series of changes described above have a more or less
difference of time between the decidua serotina and the decidua
Vera, viz., in the formerpthey may be followed up vigorously
up to the end of the second month "of pregnancy, though in the
third "month they suddenly decrease, whereas in the latter
such changes may be demonstrated even one month later.
 
THE HISTOLOGICAL STRUCTURES AND THEIR FUNCTIONAL
SIGNIFICANCE (SOME REFLECTIONS ON LITERATURE)
 
In the preceding chapter I have given a somewhat minute
account of the delicate histological structures of the various
important cell groups which exist in the placenta and the decidua vera at different periods of pregnancy. Now, on a perusal of the observations given therein, it will be found that as
components which are common to the various cell groups there
are 1) plastosomes, 2) lipoid granules, and 3) vacuoles. As a matter of course the degree of the appearance of the three kinds'of
components and their distribution in which they are present
vary infinitely as the kind of cells differs or according to each
individual cell. However, that which exercises the most important influence over the shape and formation of the cell is
chiefly the lipoid granules and vacuoles, of which the latter
often appear in a very great number and occupy the whole body
of the cell, thus giving the cell a highly foamy appearance or
a honey comb structure. The cell which has fallen into such highly vacuolar formations makes one feel, at a glance, that it has
presented a phenomenon of collapse due to the regression of
the cell concerned, as some observers ‘are apt to conclude quite
hastily. However, as, on a careful examination of it, it is found
that, in spite of the high degree of changes. shown by the cell,
there are demonstrated for the most part within the cell body
the plastosomes which are deemed an important active element
in the functions, and also in consideration of the normal structure of the nucleus and of the fully stained conditions of the
cell body, there is no doubt as to the cells being alive. And even
if it should be conceded for a while that the cell having the fully
stained vacuoles as described above is the indication of a kind of regression, who could explai11 the reason why this kind of ‘regressive’ cell actually appears in so high a degree within the tissues of the placenta ‘and the decidua at a certain period of
pregnancy, and especially in the first half of pregnancy when
the tissues should grow in a most vigorous manner? Therefore, I am confident that not only is it wrong to deem such
vacuolar formations a death phenomenon of the cell, but also
they should rather be taken for a quite significant phenomenon
which shows a certain function of the cell concerned. And,
as regards the actual existence of such a function, I am inclined to assert from their closest resemblance to the structures of
many other glandular cells, as a result of my histological observations, that a secretory function is existent in these kinds
of cells. However, as the problem is of such a provisional
character I will, for the present, reject all hasty assertions, but
instead will consult literature Widely and make generalreference
to the previous interpretations of many authors on the structures and secretory processes of the various glandular cells in
the organs in -which secretory functions are definitely known,
so that the most deliberate considerations can be given my
histological observations and their functional significance, which,
being compared and discussed under impartial criticism, it is
hoped, will help toward making the original nature of the functions clear.
 
Since the relations between glandular histology and secretory functions were early dwelt upon by R. Heidenhain (’68,
’75, ’80) with his penetrating eyes, the subject has aroused the
interest of many excellent physiologists and histologists, and
the studies of’ the subject have since followed so quickly one
after_ the other, that it would be difficult to enumerate them
here. The following are the principal authors who have studied
the subject, and the materials chosen by them for investigations
were chiefly pancreas, salivary glands, gastric glands, lacrimal
glands, skin glands, and pelvic glands, all of which are usually
known as representative glands in many kinds of animals classed
above the amphibians: Schultze, Fr. E., ’64 and ’67; Langhans,
’69; Pfiiiger, ’7 1; Schwalbe, ’71 ; Ebner, ’73; Nussbaum, ’78 to ’82;
516 GENCI-IO FUJIMURA
 
Ebstein and Griitzner, ’74; Lavdowsky, ’76; Langley, ’7 9 to ’89;
 
Mathews, ’80; Klein, ’82; Biedermann, ’82 and ’86; Flemming, ’82;_
 
Kiihne and Lea, ’82; Nicoglu, ’93; Altmann, ’94; Galeotti, ’95;
Krause, ’95 and ’97; Muller, ’96 and ’98; Solger, ’96; Zimmermann, ’98; Held, ’99; Maximow, ’0l; Noll, ’01; Fleischer, ’O4;
Heidenhain, ’07; Babkin, Rubaschkin, and Ssawitsch, ’09.
 
I will not go to the trouble of giving a detailed accountof each
of the results of these research works, but will confinemyself
to summarising the main points of their investigations respecting
the structure and secretory phenomena of glandular cells, which
are most essential to my studies, and refer to the original works
for details.
 
In the first place, the structure of the glandular cells having
a duct, or externally secreting glands, greatly differs, as is generally well known, according as they are serous or mucous. The
serous cells have an exceedingly large number» of granular
bodies, and consequently their characteristic is that they are
generally dark. Thesegranular bodies are generally known as
Cl. Bernard’s secreting granules. The .relation which the latter
has to secreting functions has been generally recognized by
 
many an interesting research work since that of R. Heidenhain, _
 
and it will be noted that Heidenhain, having observed a kind
of slender thread-like structure which exists close to the basement membrane, of the glandular cell of a dog’s pancreas, for
the first time drew general attention to a peculiar sort of organic
structure which is existent in the glandular cell. This kind of
 
. thread-like structure was demonstrated also in the salivary
 
ducts and convoluted uriniferous tubules in after years, and it
cannot be anything but M. Heidenhain’s so-called ‘Basalfilamente’ or our plastosomes. '
 
Below I wish to give a general outline of the changes appear-.
 
ing in these organic tissue elements of .the glandular cells which
will follow the secretory functions.
 
Now, at first, it is universally agreed by every author that
secretory granules increase or decrease according to secretory
functions. According to the result of the close examination
with respect to such correlation, conducted chiefly while in a fresh condition, of the pancreas of the rabbit, the oesophagus glands
of the frog, and the gastric glands of the water lizard, by Langley
(’79 and ’89), whose exposition of the correlation is best authenticated, it will be noted that during suspense of their functions glandular cells are generally glutted with secretory granules,
whereas as secretion begins the granules gradually decrease and
disappear, in consequence of which in each cell will appear a
sharp demarcation between the homogeneous wide outer layer
and the remaining granular inner layer. This observation of
Langley has been repeatedly proved‘ by many other authors in
many other glands, and its validity except in a small number of
cases, has been recognized by nearly everybody.
 
For convenience, I defer to a later section a minute explanation
of the functional significance of the thread-like production which
is found in the basal part of glandular cells. n .
 
Even in mucous cells it has been universally acknowledged
by many authors since F. E. Schultze (’64) that there are granular bodies in large numbers at a fixed period of secretion, and
at the time when secretion is very high these granules gradually
disappear asin the serous cells (Langley, ’7 9 ; Biedermann, ’82). It
seems therefore that in the forms of secretion formation mucous
cells agree, for the most part with the serous cells. However, the
reason Why both differ Widely in their structure is that in the
latter the secretion is, for the most part, speedily drained into the
glandular lumen at the time of secretory function, whereas
in the mucous cells it is formed withinthe cell bodies, besides
being stored up there for a certain period, thus giving the cells
a peculiar structure and a characteristic clearness.
 
In short, in the aforementioned two kinds of glandular cells,
the large quantity of secretory granules always to be seen in
both during suspense of secreting functions disappears, by degrees
as the functioning begins. In View of this fact, we have no
doubt whatever that, at the time of secretion, the granules
always play an indispensable part as the mother-ground for
the secretions and, since secretory granules are generally deemed
a solid production, according to the investigations of many authors while the secretions are mostly fluid, it follows that it would be no
great error to take it that, viewed simply from the histological
standpoint, the so—called secretion, after all, _means, the liquefaction of secretory granules. However, the modes of liquefaction are,
according to my view, so varied that they should by no means
be dealt with in one and the same manner, but rather there are,
roughly speaking, several forms, such as are given below,
according to the kinds of glandular cells, or according as the
cause which prompts secretion differs.
 
First form. This is observed in certain mucous cells. The
secretion is brought into being simply by the melting down and
growth of secretory granules which have developed in a fixed
degree, and, different from many other glandular cells in which
the secretory granules are mostly preproducts of secretion,
the granules here in this case show the same reaction as secretion (that is, mucin) from the beginning of their appearance
and find themselves already identical with the secretion as early
as they appear. This fact was demonstrated by M. Heidenhain in the goblet cells of the intestine of the salamander, and
it is, in general, difficult to tell definitely the time of liquefaction in what is covered by this form.
 
Second form. This is observed in many mucous cells. The
granules, while in the first stage, appear as a certain preproduct
(mucigen), and undergo a chemical change simultaneously
as they have developed to. a certain degree, and are changed
into the ordinary secretion (i.e., mucin). Mention has been
made to this effect by Biedermann (the mucous cells of the
frog); M. Heidenhain and Nicoglu, ’93 and ’98 (the skin glands
of a salamander); Altmann, ’94 (the submaxillary glands of a
cat); Maximow, ’01 (Glandula retrolingualis of a hedgehog).
 
Third form. This is often seen in ordinary serous cells. As
the functions begin, the secretory granules begin to liquefy
gradually on the periphery and, although it appears that the
granules are imbedded for a certain period in the secretion already formed, they finally change thoroughly into secretion, and
then appear as simple vacuoles within the cell bodies. The
 
‘clear halos around the granules referred to by Langley ('34), Corlier (’96) and Maximow (’01) were it seems, deemed by
these authors-an essential ingredient in the formation of glandular cells; however, M. Heidenhain with Nicolas (’92) attributed one part of them rather to artificial production, while the other
was brought into being in the form it appears in, possibly becausethe granules were reduced in size in connection with
secreting functions.‘ And in recent times the researches regarding pancreas cells, conducted by Babkin, Rubaschkin,
and Ssawitsch CO9), have proved the above mentioned views
of Heidenhain with more force and accuracy; that "is, in the
opinions of these authors, clear halos around the granules are,
after all, nothing else but secreted matter which appears as a
liquefied product of the granular substance. And that such
an image should be a sign of an important period in secretion
formation within the cell bodies will be clear in the statement
made by the three authors mentioned above on the changes
which zymogene granules undergo at the period of a pancreas
secretion: “Wir erhalteh den Eindruck, als ob das (Zymogene)
Kornchen sich allmahlich auflost, in dem es sich immer mehr und
mehr Verkleinert und in em kleines verwandelt” (p. 92).
Fourth form. According to the views of Babkin, Rubaschin,
and Ssawitsch above referred to, this presents an appearance somewhat like a modification of the third form. That is to say,
many secretory granules together with the intergranular substance concerned form themselves into somewhat large masses,
which latter slowly begin to liquefy from the periphery, and
are then gradually changed entirely into secretion in rather
large drops, to be drained out into the glandular lumen. Compared with the third form, in which each individual granule
becomes liquefied separately, this type differs from the former
in that a number of granules coagulated together in lumps
are transformed gradually into drops of secretion. This form
is distinctly demonstrated at a time when the function of pancreas cells is very greatly increased, especially by means of
stimulating the vagus nerves or of soap infusion in the duodenum, it being characteristic of the secretion at such a time
that the latter is very dense, and is rich in albumen and ferments. And the three authors mentioned above are of the
opinion that the several bodies which are revealed by this
secreting form may be compared with the small bodies which
are often known as ‘Nebenkerne,’ ‘parasome,’ ‘corpusculus
paranuclaires,’ and ‘noyau accessoir’ in the pancreas cells of
the lower vertebrates.
 
Fifth form. This points to a case in which the substance of
secretory granules changes its quality at a certain period, becomes soluble, and is only dissolved in the watery part of the
secretion alone, as was instanced by Babkin, Rubaschkin, and
Ssawitsch, in the experiment of the pancreas secretion after
pouring acid in the duodenum. As a proof thereof, the secretion
always shows in this case the same coloring reaction as do the
zymogene granules.
 
The three forms (the third to the fifth) described above are
together met with in the pancreas cells, and it deserves special
attention that accordingas the cause differs for the rise of secretion, even in one and the same glandular organ, there is a
difference in the forms of secretion, and consequently in the
nature of the secretion produced.
 
Sixth form. Certain secretory granules sometimes have
two extreme developments. As an instance, M. Heidenhain
observed the skin glands of a salamander and he found that,
as the development of the granule reaches a certain degree, one
part of it is liquefied and passes into a viscous secretion, while
the other goes on growing in size, and is perfected into the characteristic poison grains.
 
Seventh form. A certain organic structure is presented in
the secreting granules; at the beginning it is not different
 
_from ordinary cases, and yet as a certain development is
 
accomplished, every granule is divided into a crescent—shaped
section (Kapuze) which is stainable, and into an unstainable
section (Trager) within the crescent-shaped section, thus forming
the ‘Halbmondkoperchen’ so termed by M. Heidenhain. This
latter as it grows in size is considerably enlarged, especially
in the Trager, and consequently the Kapuze is flattened gradually
and is only stuck like a plate on its one side. Then the Trager is at last dissolved altogether and is changed into secretion,
while at the same time the Kapuze is also condensed, and forms
itself into secondary granules, later on to be drained out along
with the secretion, thus bringing about an entirely granule free
condition of the cells. This form of secretion was first detected
and examined closely by M. Heidenhain in the pelvic gland of
a salamander and in the lacrimal gland. Subsequently, Nicolas
(’92), in a man’s lacrimal gland, Held (’99), in a rabbit’s submaxillary gland, and Fleischer (’O4), in a coW’s lacrimal gland,
observed and proved the appearance of the crescent-shaped small
bodies described above.
 
The above does not cover all the forms of granular liquefication at the time of glandular secretion, and yet it will be
quite clear how varied the modes of liquefication are. . "
 
Now, I will discuss a little further the origin, and therefore
the manner in which supply is made of secretory granules,
this problem being the second in importance with respect to
glandular secretion. _
 
With regard to the origin of secretory granules, the problem
itself is a very difficult one indeed, but it should be noted that,
along with the sudden increase of studies on plastosomes in recent years, many authors have attempted a solution of this
troublesome question.
 
Below I give a general account of the result of these researches.
Generally speaking, every author equally agrees in the argument
that every glandular cell always has within the cell body plastesomes as constant ingredients and, though the quantity and
arrangement of the latter are certainly varied, it is the usual condition that while the serous cells are in a state of rest the numerous
plastosomes are chiefly arranged in rows along the long axis of
the cells. These plastosomes, however, generally decrease in
quantity considerably during the period of secretion, especially
when the cells are filled, and they are then found largely, close
to the basement membrane of the cell, while near the lumen,
they are either entirely absent or, if they are found, they are
 
between the granules in a very small number. And in mucous
cells, in contrast to serous cells, the plastosomes are found largely
522 GENCI-IO FUJIMURA
 
near the nucleus, though some lie scattered in the protoplasm
between the secretory granules, all being arranged in an irregular
order. With regard to the functional significance of the plastosomes contained in these glandular cells, there are various
theories, such as the theory of secreting mechanism by Benda
(’O3, p. 780), that of water-secreting apparatus by M. Heidenhain (’O7), and that of prop system by Bruntz (’08); however,
these are either the historic ones, having been refuted
experimentally by Meves and Regaud (’08) already, or mere
assumptions.
 
What is believed by a great majority of authors at present is
that plastosomes are very closely related to the formation of
secretory granules. And the first man who published his views
with'regard to this was Altmann (’94), who’ thought that his
so-called ‘vegetative Faden’~a greater part of which agrees with
our plastosomes of to-day~being split up in small pieces are
formed into granular bodies in large numbers and make the
beginning of secretory granules. Quite recently the researches of
Laguesse (’99 a, b, ’05, ’11), Regaud (’O9), Regaud and Mawas
(’09), Hoven (’10, ’11,-’12), Champy (’11), Schultze (’11), have
followed one after the other, and, though their observations may
differ a little from one another, either in trifling points or in the
form of description, they none the less fall entirely into line with
Altmann’s View that the formation of secretory granules has
its origin.in plastosomes. And, moreover, the fact that, as is
generally acknowledged, the number of plastosomes in glandular cells always increases or decreases according to the changes
of secreting functions is nothing if not forcibly proving the validity of such a theory. l
 
However, this very theory is not without objections. M.
 
.Heidenhain, Mislawsky (’11), and Levi (’12) are those who
 
are opposed to it. Especially M. Heidenhain, taking his stand
on the ‘Protomeren-Theorie’ which he set forth, states that
secretory granules should have their origin in extremely faint
and extraordinarily small bodies in the protoplasm which are
beyond our sight; these bodies growing up and increasing
should gradually develop into the ‘smallest granules-—his ‘Primargranula’—which are seen microscopically to gradually
bring about the growth of definite secretory granules. Thus
it seems he denies the-histogenetical correlation between plastosomes and secretory granules. His theory, though most dex-_
terously proposed on the most profound proofs, is after all a
mere hypothesis. Besides, in consideration of the following
quotation, it will be quite clear how he holds the views that his
so-called ‘Primargranula’ have a close. relation with the genuine
cytomicrosomes in their formation, and that the _latter do
correspond to a section of his ‘Basalfilamente,’ and, further, that
the filaments are identical with F1emming’s M.itom:
 
Ich bin daher mit Solger der Meinung, dass auch in den serosen
Driisenzellen die Basalfilamente Teil eines Fadensystems sind, welches
nach der Bezeichnungsweise Fle_mming’s dem sogennanten Cytomitom
zugehoren wfirde. . . . . Nicht ganz ausschliessen darf manjedoch
zur Zeit die Moglichkeit, dass die Drfisengranula evéntuell von den
genuinen Plasmamikrosomen sich ableiten, welche nach unseren allgemeinsten Erfahrungen immer innerhalb der Protoplasmafilamente liegen,
also verdichtete Teile feiner Fadchen sind. . . . . Da nun die
Korperchen beiderlei Art (Primialrgranu-lis und genuine Mikrosomen)
morphologisch schwierig unterscheidbar sind, so kanneine verwandschaftliche Beziehung zwischenbeiden zur Zeit wenigstens nicht abgelehnt wervden, besonders da wir fiber die positive Bedeutung der genuinen
Plasmamikrosomen noch sehr im Unklaren sind (p. 390).
 
And since it has already been clearly, proved by the researches
of Meves (’07) that F1emming’s Cytomitom agrees with our
plastosomes, it would appear that M. Heidenhain does not only
maintain the View that his ‘Basalfilamente’ exists as a watersecreting apparatus as mentioned above, but at the same time
also supports, instead of disproving, the argument which regards basal filaments as being the matrix forthe formation of
secretory granules, as Altmann and others do. As regards
Mislawsky’s view, it will be noted that he, in line with ‘Levi,
takes the ground that as between plastosomes and secretory
granules there were no conspicuous conditions to be detected in
support of the existence of a formative relation between the two.
However, anent Mislawsky, it will be noted that the invalidity of such a view has been exhaustively pointed out by a Belgian
cytologist, Duesberg, in comments noted for their profundity and thoroughness. The following phrase is there employed by
him: “Ein negatives Resultat beweist nichts gegen eine Reihe
positiver Resultat und man kann nur schliessen, dass Mislawsky
die Bilder nicht beobachtet hat, die seine Gegner unter Augen
hatten” (p. 785). This should incidentally prove to be a
pertinent comment on the theory of the excellent Italian
author, Levi.
 
If we summarize the observations of the various authors
respecting the structures and functions of the glandular cells
described above, we may enumerate as constituents of the glanduar
cells, 1) plastosomes, 2) secretory granules, and, 3) secretions
(vacuoles), besides the protoplasmic stroma proper, and it would
be superfluous to state that of these constituents secretory granules
have a directly important relation to the glandular secreting
functions. The secretions are nothing else than a liquefication
or modified product of the latter and there is no alternative but
to assume that the secretory granules, once lost at secretion,
take their matrix mostly from the plastosomes, which latter,
being split up and separated in small pieces, gradually meet the
deficit so caused. Thus, the real state of glandular secreting
functions is already a thing which can be largely followed up
and made clear by means of minute histological investigations
to-day.
 
Also the histological studies of the ductless glands—~internally
secreting cells—have become very active of late years, and,
especially among those which have been carried on by the methods
of plastosomic study, we may enumerate the thyreoid and parathyreoid glands, suprarenal capsules (chiefly its cortex), Langhans’ islets of thepancreas, and the ovary. Of these organs,
the ovary has been used more often than the rest as the object
of study, and consequently, comparatively speaking, much is
known about it. I will therefore give a general summary of
the observations of the various investigators respecting this
organ, consider its structure and the relations of its internal
secretory functions, and then glance at the structures of the
other organs, thus contributing toward a histological account
of internal secretion in general.
 
 
That the corpus luteum is a kind of internally secreting organ
(from the histological point of view) was advocated by Prenanas early as 1898 and by Born in 1900. Subsequently, the argument has been advanced with more certainty by a close
histological study conducted by Regaud and Policard (’01),
Fr. Cohn (’O3), Mulon (’09), Athias (’l1), Van der Stricht (’ 12),
Tsukaguchi (’12, ’13), and Levi (’13). And the main grofind
of this argument lies in nothing but that the luteal cells contain as formative ingredients of the cell bodies plastosomes and
lipoid granules, and often demonstrate a very large quantity
of vacuoles which may be deemed their secreted matter, and
also that the close correlation between these ingredients functionally is plainly apparent in the same manner as it is seen in
external secretory cells. Of the various ingredients mentioned
above, lipoid granules certainly have the most important significance in internal secretion; however, since the latter is not
only characteristic of luteal cells, but is also widespread among
the other kinds of internal secreting cells, Tsukaguchi has
already argued that it would be proper, in view of its functions,
rather to compare them with the secreting granules of ordinary
glandular cells. '
 
In the next place, Cohn first regarded the vacuoles in a rabbit as a secreted matter of the luteal cell, and he saw them simply
as a dissolved product of lipoids; subsequently Tsukaguchi also
studied the same animal, and likewise deemed them a modified
product of lipoids. However, vacuoles differ exceedingly in the
degree of their development in all kinds of animals. For instance, Van der Stricht did not notice any vacuoles in the
luteal cell of a bat, and subsequently Levi’s observations
regarding the same animal nearly agreed with those of Van der
Stricht. _ In the guinea-pig, however, Levi noticed a small number of vacuoles, which he attributed to a retrogressive phenomenon of the cell concerned, and he stated that this phenomenon, by means of a chemical change of lipoids following
it, could cause possibly the substance of the latter to be
dissolved by the benzol and xylol which had been used by
him, as clearing media. In short, whenever the vacuoles appear, the lipoid granules first make their appearance as
their forerunners, and the former pass into the latter in succession, as has been entirely agreed upon by many observers.
 
With regard to the origin of lipoid granules, the Zoyas
(’91) pointed out that there was a certain quantitative relation
between granules and plastosomes, and this fact was acknowledged by Mulon, Athias, and Tsukaguchi, though Levi alone
tried to deny it, as in the case of external secretory granules.
 
With regard to the secreting phenomena of luteal cells, Van
der Stricht argued that in the order Chiroptera it was possible
to divide them into two forms, viz., serous secretion and lipoid
secretion. By serous secretion is meant that the follicular
epithelium, being the antecedent of the luteal cells, secretes
liquor folliculi, and, according to him, the Graafian follicle,
after rupturing, still keeps on secreting in this manner for a
fixed period, it being characteristic of this secretion that in the
peripheral part of protoplasm of the young luteal cell some
serous infiltration appears, and for that reason gives that part
generally a somewhat transparent appearance. Already at this
period a large quantity of small lipoid granules appears within
the cell bodies; however, since these granules do not as yet per
‘form any functions, he called this stage the serous secreting
 
period of the luteal cells; then, as the ovum settles,.the corpus
luteum has already reached its highest degree of development,
and he termed it the second stage of corpus luteum formation.
 
At this stage the cell body is already filled with numberless
lipoid granules, which, undergoing a chemical change, cause the
cell body to keep on discharging secreted matter until the end
of pregnancy. This is what the lipoid secretion means. This
theory seems to have been afterward accepted in the main
also by Levi. However, the condition is entirely different in the
Rodentia, and especially in the rabbit. According to the observations of Cohn and Tsukaguchi, lipoids chiefly appear in a high
degree only in the early part of pregnancy, then disappear rather
speedily. In the second half of pregnancy the lipoids change
into vacuoles almost as transparent as water, the cell bodies present a highly distinctive vacuolar structure, such condition being still more conspicuous toward the last period of pregnancy. N ow
comparing this with what is observed in the Chiroptera
mentioned above, this period of lipoid secretion, so-called by Van
der Stricht, in the rabbit passes away in a comparatively short
time, and then slowly passes to the stage of the characteristic vacuolar image; thus, it appears, it presents a certain
stage of secretion which is peculiar to itself. In short, it is interesting to note that, in consideration of the changes in the
forms of secretion in external secretory cells, the structure, and
therefore the form in the secreting functions even in the same
luteal cells, differ according as the class of animals differs.
 
That the interstitial cells of the ovary possess the same internally secreting functions as luteal cells, by reasongof the close
resemblance which they bear to the latter in shape and structure,
has been universally acknowledged in the researches made,
in various kinds of animals, including the Rodentia, Chiroptera, and Carnivora, by Regaud and Policard (’01), Limon (’02,
’03), Fr. Cohn (’03), Regaud and Dubreuil (’O6), Mulon (’11),
Athias (’11, ’12), Van der Sticht (’12), Tsukaguchi (’12, ’13),
Levi (’ 13) . Now, according to these observers, the interstitial cells
also contain, as do the luteal cells and many other glandular
cells, important constituents, such as plastosomes, lipoid granules, and vacuoles. The vacuoles are especially very plentiful,
and they, for the most part, present a minute, delicate, and
peculiar vacuolar image, the protoplasm proper being barely
noticeable around the nucleus. The lipoid granules, as compared with the luteal cells, are generally small in quantity and,
moverover, it is sometimes difficult to detect them. It is
customary for the lipoid granules more or less to increase in
quantity at the time of pregnancy. It has been equally
acknowledged by many observers that the lipoids of the interstitial cells generally appear for a comparatively short period,
commonly fade away in color and change in quality speedily,
thus gradually passing into the vacuolar substance. And then,
many authors, except Levi, have proved and recognized, even
in this case, that plastosomes have a direct relation in the
formation of lipoids.
 
 
Entering into details, Mulon stated that in the rabbit the
plastosomes, granular in form at first, change into minute
siderophil granules, and then diffuse siderophil substance, and
the lipoids will be formed from the latter. Athias (’12), who
examined a newborn bat, also seconded the argument of Mulon
for the most part, and argued that plastosomes produce the
lipoid first at their center and accumulate it there, and in support of his argument he stated that occasionally the cortex,
which has the same staining properties as plastosornes, could be
detected around the lipoid granules. Tsukaguchi certified to
an intermediate type of granules between the plastosomes and
the lipoid in the young interstitial cells, thus arguing that the
granular plastosomes develop and grow in size directly into the
lipoid granules, as are seen in the case of the luteal cells. In
short, the various investigators have not as yet come to an
agreement in their views as to the correlations between the
two, and yet it has been universally acknowledged by them
that as the cells grow and increase and the lipoids or vacuoles
appear plentifully, the plastosomes decrease in quantity in
inverse ratio.
 
With regard to the organs other than the ovary, Mulon (’10
a, b) closely examined the suprarenal capsules of a guinea-pig
and rabbit, and stated that by the conglutination of the granular plastosomes was produced directly a ‘substance (possibly
our lipoids) which has affinity for osmic acid (osmophil) or ironalum-haematqxylin (siderophil), and is introductory to the
formation of a vacuolar secreting matter to follow. Celestino da
Costa (’07), Champy (’O9), and Colson (’10), also having experimented on the cortical cells of the suprarenal of a cat, guinea
pig, toad (Bombinator) and bat, have proved the same fact as
 
above. Bobeau (’11) also argued that when the parathyreoid
glandular cells of a horse form a certain effective product the
plastosomes should play an important part. And, besides, Engel
(’09), Mawas (’11), and Schultze (’11), each demonstrated the
plastosomes in the thyreoid and parathyreoid glands of a man, a
rabbit, and a frog, and, according to Duesberg, it was stated
that the plastosomes could be detected in the Langhans’ cells of the pancreas. It should none the less be stated that a majority of the facts enumerated above are merely preliminary.
Many future investigations must be looked forward to for a
further enlightenment of the secretion of these organs.
 
In summarizing the histological knowledge We have at present of the internal secretory cells described above, almost every
cell has, as its constant ingredients, plastosomes, lipoids, and
vacuoles. Now, the plastosomes are not regular either in their
shape or‘ arrangement while the lipoids are not quite regular in their size, quantity, and color, but the smaller ones
bear a resemblance to granular plastosomes, while the
larger ones, agglutinating with one another, form larger
fatty droplets. The contents of the vacuoles probably consist
of watery, transparent droplets, which are separated from one
another by a very thin partition wall. The cell body should
present a more or less conspicuous alveolar structure in proportion to the quantity hf vacuoles contained. The quantitative correlation by which these formative ingredients are
connected to one another is not free from considerable variations. Occasionally only one or two of them exist to the absolute exclusion of all the rest._ It must be very often the case
that such phenomenon-may. be partly due to the difference in
the order of animals chosen for the subject of study and partly
to the functional relation of the cell concerned. In short, it
may be said that the various formative ingredientsdescribed
above as being seen_in internal secretory cells constitute equally
necessary constant elements, the same as with external secretory cells, as has been minutely dwelt upon previously.
Now, it is a marvelous sight indeed to compare, histologically
these two kinds of cells, and to look at the perfect agreement,
not only in their structures, but also in the various histological
changes which follow their functions. On this score, I am convinced that should there be a structure like the two kinds, of
cells described above, besides the functional changes which
very nearly correspond to the above, it would be no error to
bring such cells under the category of glandular cells, regardless of the existence of a duct in them. And, if we look at the various cells of the placenta and the decidua, we will find that
all of them are well furnished with various conditions which
mark the glandular cells above referred to, and that naturally we
should assert the existence of secretory processes in them , also.
In the following section, I will give a detailed account of. the
secretory phenomena of the various cell groups.
 
THE PHENOMENA OF INTERNAL SECRETION IN VARIOUS CELLS OF THE PLACENTA AND DECIDUA
 
It is too plain to need argument that in-all cases the real state
of the life processes of any cell cannot be made clear unless all
the phenomena in the living condition of the cell concerned be
followed up closely with the microscope. However, since it
is certainly difficult to attain such an object by the histological method employed by us at the present time, by noting the
phenomena of internal secretion it is possible to denote each of
the extremely varied structural images obtained from the preparations fixed and stained as indicating a certain period in the
phenomena of secretion; to compare carefully and consider the
correlations between the different periods, and thus to infer the
whole of the process of secretion. Therefore, I must ask the
reader to take this point into consideration.
 
1. The phenomena of «internal secretion in the syncytium layer
 
Now, at first, in figures 1 and 2 only plastosomes are present, M
and lipoid granules and vacuoles are entirely absent, so that
we may conclude that this shows the early stage at which secretion is not yet in appearance or when secretion is at rest. In
the next place,‘ in figures 3 and 4, more or less lipoids appear,
and vacuoles are either barely found at one part or not formed
as yet; the lipoids, in general first appear on the superficial
 
.layer, at which place they tend to grow up and increase gradu
ally. The plastosomes have decreased considerably in quantity
especially in figure 4. The last two figures may be taken as the
early stage of secretion in the syncytium layer, and as it passed to
the subsequent stage, a large number. of vacuoles, viz., secretions, appear besides the lipoids. The vacuoles later on keep
increasing, while, on the contrary, the lipoids decrease in
quantity, and, moreover, of these vacuoles those which are
near one another unite into vacuoles of various sizes, and it
will be seen that the surface vacuoles of the latter ultimately
rupture and open upon the surface of the syncytium layer.
The process of secretion described above may be followed in
figures 5 to 7. Should this process continue and reach its
highest degree, such structural images as are shown» in figure
8 would be probably brought about in the end! What is pecu—
liar in these various stages when secretion is very high is that
plastosomes are detected. In the next place, what is shown
in figure 9 is taken, similarly to what is in figures 3 and 4, for
a comparatively early stage of secretion. However, the former
differs more or less from the latter in that already a somewhat
large quantity of vacuoles is noticeable in it. And, especially,
the vacuoles are chiefly arranged close to the Langhans’ cells.
Figure 10 demonstrates on one side a large quantity of plastosomes and on the other a region where no plastosomes are to
to be found. This region presents, as mention has been made
already, a foamy structure which can be detected only by careful attention. Figures 11 and 12 each clearly demonstrate plastosomes, besides a large quantity of vacuoles and a small quantity of lipoids. That is to say, in figures 9 to 12 it is always
easy to demonstrate plastosomes at different periods of secretion,
and therefore the various periods of secretion shown therein
may be differentiated from those given in figures 5 to 8, though
it is not easy to decide what correlations these stages have periodically between themselves in point of secreting ‘functions.
However, according to the various images described above, it
is deemed practicable in the main to arrive at the following
presumptions with respect to the phenomena of secretion of
this cell layer:
 
a. At a time when function of secretion has not yet begun,
the chief ingredient of this layer is plastosomes, whichare found
in a very large quantity; however, as the function begins,
they suddenly decrease in quantity, and at a certain period, especially when lipoid granules are exceedingly plentiful, they
entirely disappear. . It has already been explained how this lack
of plastosomes is not the result of the want of skill in the
making of preparations.
 
b. As the function begins, lipoid granules first appear conspicuously, especially at a place which is close to the superficial layer, and then vacuoles appear. Sometimes both can
appear simultaneously at a comparatively early stage (fig. 9).
 
c. The direct relations between the lipoid formation and
plastosomes , could ‘not be ascertained in my preparations. However, the origin of lipoid. granules was found in an extremely
small granular body, and on the other hand it is clear that
there is a tendency for the plastosomes either to decrease more
or less in quantity as function of secretion increases or to entirely disappear. , .
 
d. The transparent halos which are sometimes found around
the lipoids give the latter anpappearance of being the contents
of vacuoles, and by reason of such a condition we are led to believe that a certain intimate relation exists between lipoids and
the vacuolar formation (figs. 7, 9, and 12).
 
e. However, we cannot as yet positively state whether or not
all vacuoles without exception have an intimate relation with
lipoid granules such as is described above. For instance, I
cannot definitely declare whether the formation of the extremely
delicate foamy image such_ as is seen in a part of figures 8, 10,
and 12 has been the result of the lipoid granules while in the
earliest stage of lipoid formation, that is, while as yet in a stage
in which they are exceedingly small, having changed their
quality, and caused such small vacuoles to grow in groups,
or whether as Mulon quoted before, has observed withirespect
to the ovarian interstitial cell, at the period of his ‘diflused
siderophil substance’ (though it is still beyond my power to
prove that such a period could appear in the syncytium layer),
the substance has, instead of forming lipoids directly assumed
a vacuolar formation. It is for future investigations to solve
such a question.
 
f. All vacuoles gradually unite, and it appears that they
possibly make a kind of canal system running irregularly and
crosswise within the syncytium layer, and some of them distinctly
open their mouths in various places on the surface of the
syncytium layer, thus it is apparent ,that their contents, their
secretions, are drained out into the maternal vessel of the intervillous spaces. And, as is seen in figure 11, the blood corpuscles which are noticeable within the syncytium layer may be
rightly taken for the mother’s corpuscles which have accidentally
gone into the canal system mentioned above, which would in
turn prove the existence of the latter.
 
g. The secreting function is at work from the beginning of
pregnancy to the end of the fourth month, though it is most
active in the second and third months.
 
2. The phenomena of secretion of the Lomghoms’ cells
 
The protoplasm in the Langhans’ cells which are still small
and should be deemed comparatively young contains plastosomes
only (figs. 13 to 16); however, as the cells reach a certain size
the lipoid granules appear (figs. 4, 11, 12, 17, and 22). The
latter have developed from extremely small granular bodies such
as are Visible in figures 9 and 21, and their number is not very
large; the vacuoles appear in a very conspicuous manner, and it
seems that these have also grown into what they are comparatively speedily from a very minute form, it being clear that the
larger. of them have been brought into being by the agglutination and joining together of some of the vacuoles. And,
while the secreting process is in progress, it seems that lipoids
play a directly essential part; how they change their quality
and liquefy from the periphery, and thus gradually pass into
vacuoles as in the syncytium layer, can be very clearly seen
in figures 12, 23, and 24. The loss of lipoids which keeps going
incessantly by such vacuolation is made good by fresh formations elsewhere, and thus, the same process being repeated, the
vacuoles go on growing in number and size simultaneously as
the cell appears more and more to increase in its capacity, though the preparations I have are still very poor to prove this
positively. However, the fact that, as mentioned above, lipoids
have their origin in very small granular bodies and that
plastosomes considerably decrease in quantity as the cell grows
in size and therefore its functions are promoted (please refer to figs. 13 to 21), cannot but be taken for having proved
that V plastosomes, owing to their quantitative relations, take
part in the lipoid formation and, if this deduction be practicable.
it would follow that the large group of plastosomes which
makes its appearance in an especially limited section, as is
seen in figures 3 and 9, should not be without significance for
the new growth and supply of lipoids. In short, the phenomena of secretion of Langhans’ cells, in general, are not very
active and yet the cells in the Langhans’ islets are somewhat
different, and it seems the functions are very active in this
part, so much so as to make it a feature of these cells that they
present a very large and highly vacuolar formation (figs. 21,
22, and 26).
Since the Langhans’ cells always have on the surface a comparatively conspicuous border membrane, there is no alternative for the contents of vacuoles, viz., secretions, but to pass
through this membrane and be drained into the villous tissues, and
they are therefore possibly bound to be ultimately absorbed on
the side of the embryo. However, since the part like the Langhans’ islets where the functions are necessarily very active is,
as is Well known either mostly wrapped up in the decidual
tissue or exists within the intervillous spaces, floating directly
in the m1(:ther’1s blood, it is posisible that the secretions coming
rom sue a p ace are absorbe on the mother’s side. Moreover, the large number of vacuoles which is found in a part
where the Langhans’ cell layer comes in touch with the syncytium cell layer as in figures 9 and 12, judged from the position
they occupy, has been temporarily denoted by me as forming
secretions of the syncytium layer and so described in the
previous paragraph; however, I am afraid nobody can say for
certain that it is so. If we suppose that the secretions are
brought forth by the Langhans’ cells, who may say they will not come out into the intervillous spaces together with those
of the syncytium layer? In a word, since the Langhans’ layer is entirely closed against the mother’s body by the syncytium layer in the early stage of pregnancy, it would follow that the
secretions are entirely in the service of the embryo, but after
that it _is probable that a part of them are taken also by the
mother’s body. .
 
The function of secretion of the Langhans’ cells, just like
the syncytium layer, is active in the main almost from the
first stage to the end of the fourth month of pregnancy, though
in the second and third months it is very active, suddenly
subsiding with the fifth month. In the Langhans’ islet it continues still longer and commonly gradually subsides after the
sixth or seventh month. T
 
The epithelium of villi is located between the circulation of
the mother’s body and that of the embryo. and it is for this reason presumed that it must be an organ which takes nutrition
for the embryo, as has been commonly held in literature, but
that such is a groundless assumption must be quite clear from
my histological observations given above. And,_besides, there
are some important reasons which prove the utter fallacy of
this theory. It is in the first to third months of pregnancy
that the growth of the epithelium of villi is most active. If
the functions of the alimentary organ for the embryo be assigned to it, the. epithelium of the villi should go on developing most
vigorously, but the fact is quite the reverse, and it retrogrades
and becomes thin in the second half of pregnancy, and accordingly the decline of functions is brought about. This is one of
the absurdities. And in the eighth month of pregnancy, when
the embryo calls for a still greater increase in the supply of its
nutrition the capillary blood vessels of villi increases suddenly,
as was mentioned above, and early in this stage the epithelium of villi becomes remarkably regressive and falls into decay,
so that the embryonal circulation -of the villi is separated
from that of the mother only by a thin membrane like endothelium, undoubtedly it being quite easy for both to allow the
interchange of materials between them. In other words, the particular organ which is needed for the absorption of nutrition
for the embryo first makes its appearance in a perfect condition
only after the epithelium of villi retrogrades and becomes thin.
on this score I am led to believe that the epithelium of villi is
simply an organ of internal secretion, and that the ground is
extremely weak for the argument, which treats it as an organ
to take nutrition for the embryo, as has been generally conjec-.
tured in the past.
 
3. The phenomena of internal secretion in the stroma cells of villi
 
The smallest of the. stroma cells of villi is simply a ballshaped cell which is comparatively rich in protoplasm, and
within the cell body there is a large quantity of plastosomes
(fig. 27), but presently a somewhat large quantity of lipoid granules or vacuoles having various sizes appears within the cell
body (figs. 28 and 29); and" subsequently, as the cell grows in
size the chief ingredients of the cell body will be plastosomes
and vacuoles, while the appearance of the lipoids is not very
distinct. The image such as is seen in figure 34 is very seldom
met with. On the contrary," however, the vacuoles may be
deemed the almost constant ingredients of each cell, and
especially as the cell developes and grows in size they increase
the more in size and quantity, and present a highly foamy
structure which is characteristic of this kind of cell. Now,
if we consider the correlations between the different constituents mentioned above, it will be found first that in these
cells the plastosomes are stained comparatively easily, and are
therefore very distinctly detected in each cell; and as regards
 
its quantitative relations, it will be noted that there is not the
 
least tendency in the plastosomes to decrease in quantity, even
though the functions increase and the cells enlarge, as was seen
in the epithelium of villi described above. On the contrary,
the plastosomescrowd together in large numbers in the various
protoplasmic sections of cell bodies, and they present the appearance of a new growth and multiplication in the sections
concerned (figs. 30, 31, 32, 33, 36, and 38). The only exception is that when the quantity of lipoids contained in the cell body is remarkably large, the plastosomes decrease more or
less remarkably in quantity (figs. 28 and 34). The lipoid
granules, as mentioned above, do not appear in very large
numbers and, since they arise from very small granular bodies, it
is very diflicult to clearly discriminat_e the latter from the ordinary
granular plastosomes (figs. 28, 29, 31, 36, and 37). Therefore,
in consideration of this fact and of the quantitative relations
between lipoids and plastosomes as described above, I am inclined to trace the mother-ground of the lipoid formation
in the plastosomes. Then, with regard to the vacuolar formation, we may infer from the conspicuous halos which often appear around the lipoids, or from a phenom_enon in which the
lipoid often occupies the position of a nucleus within the vacuole (figs. 29, 34, and 36), as in the case of the epithelium of
 
villi as described above, that the vacuole should of necessity»
 
be the liquefied product of a lipoid. In short, it may be stated
that the secreting phenomena of these cells, if looked at from
the histological view-point, are very simple indeed, and plastosomes first bring forth lipoids, which latter in turn change
into vacuoles, and the reason why the lipoids are comparatively
scant is that the period of their appearance is exceedingly short.
And, while perhaps -on one hand the contents of vacuoles,
viz., secretions, are gradually drained out of the cell body, on
the other the protoplasm and therefore the plastosomes bring
about a prospective new growth and multiplication, presumably to provide for the materials of the next secretion, and in
this manner the afore-mentioned process, as simply it may be,
is repeated and follows in succession. At different times and
in difierent places, to make a secondary or, tertiary secreting
process within a cell all the time, the cell develops and grows
in size gradually, and its structure therefore becomes extremely
complicated, and in this way I_suppose that, even in one
and the same cell body, the various periods of the phenomena
of secretion make a simultaneous appearance according to the
ingredients contained. This is a mere hypothesis of mine,
and yet since it was early refuted by M. Heidenhain that the
secretory granules of all kinds start their individual function separately as a small independent ‘organel’ within the cell,
this hypothesis of mine should not be taken exception to. And
moreover, the increase and mass of protoplasm or plastosomes
and the lipoids at different phases, all of which could be demonstrated in every part of this cell at any time, if sought for an
interpretation of their significance, will each provide a material to substantiate the hypothesis mentioned above. In this
manner, this cell, While promoting its secreting functions on
one hand, grows in size more and more, and such like relaw
tions could be recognized more or less even in the Langhans’
cell.
 
The functions of secretion in the stroma cells of villi begin
at the end of the first month of pregnancy and continue
actively until about the seventh month, though they are most
active from the second month to the sixth. And though in the
eighth’ month it appears that they suddenly subside, it will be
found at all times that it is difficult clearly to follow the
destiny of each of the cells, since it is interfered with by the
strong increase of the capillary blood vessels of villi at this stage,
as mentioned already. Since no special duct was detected, it is
difficult to tell how the secretions are removed, other than
by attributing it to osmose, as in the case of the Langhans’
 
cells, and by predestining the secretions to be absorbed by
the embryo.
 
4. The phenomena of internal secretion of decidual cells
 
If We first look at the decidual cells of the smaller type (figs.
39 to 51), we find that the chief components of the cell body in
the youngest are plastosomes (figs. 39 to 41), next appear lipoid
granules (figs. 42, 43, and 44), then follow vacuoles, it thus being customary for the great majority of decidual cells of smaller
type to contain many vacuoles and more or less lipoids besides
plastosomes. The plastosomes sometimes decrease more or
less in quantity in inverse ratio to the lipoids or vacuoles (figs.
43 and 49), but more often is it difficult to discern such relation,
and, besides, many are plastosomes Which‘ either form a conspicuous group in some part of the cell body or considerably increase in quantity (figs. 44, 48, 50, 51, and 52). The lipoid
granules arise at the beginning in a very small granular body,
whence they grow up to a certainldegree, when clear halos appear around them, and the manner in which they directly
participate in the formation of vacuoles (figs. 44, 46, 52, and 53)
is the same as what is observed in the epithelium and the stroma
cells of villi. And sometimes it occurs that the vacuolar formation appears equally at a time within one and the same cell
body, and as a result the foamy image of high degree, such as
is illustrated by figure 49, is brought into being, but this is rather
rare, and in most cases the vacuoles_ vary in their sizes. And,
besides, it is customary for the vacuolar formation in most
cases to contain at the same time groups of plastosomes or
lipoids of different sizes. In short, the smaller-type decidual cells entirely agree with the stroma cells of villi in their
structure, and, therefore, there is no need for argument that
their secreting phenomena should be dealt with in the same
manner as the latter. On this score, I will not go to the redundant trouble of touching upon the secreting process of the smaller
type decidual cells here, but will confine myself to the brief
 
H statement that the function is repeatedly performed by the
 
same methods as in the stroma cells of villi.
 
If we take a glance at the figures in the plate, it will be quite
clear that the smaller-typed decidual cells, repeatedly performing as they do the functions as described above, develop and
increase in size more and more, and passing through the
various intermediate types (figs. 52 to 54, 62 and 63) gradually, as I mentioned in the previous chapter, pass into the
larger-type decidual cells to attain the height of their growth.
Therefore, the demarcation between the large and small types
in the decidual cells is, after all, due to the difference in the degree of growth of the same kind of cells, and the smallness of the
cell should be taken for an indication of comparative infancy,
while the largeness of the cell shows that it has attained the
region of perfection in its growth.
 
The large—type decidual cells may be divided into two kinds
with respect to structure. One represents the kind of cells whose body is protoplasmic, and commonly has a large number of
plastosomes, besides more or less lipoids which are often
discernible, though vacuoles are almost absent (figs. 55 to
61). The other represents those cells whose body -presents
a highly vacuolar image, whereas the protoplasm considerably
decreases except around the nucleus, while no plastosomes are
to be found. The lipoids contained are irregular in their quantity, but more or less of them are always existent (figs. 64 to 69).
A great majority of the commonly so-called decidual cells
belong to the former, while a comparatively small number is
represented by the latter. . In the former class the structure of
the cell is entirely different from the small-type decidual cells
and my ‘intermediate type,’ so that along lines of histology
there is no indication of the existence of the process of secretion,
and although lipoids exist in smallnumbers, their quantity
quickly decreases and they go out of existence as the cell body
grows up in size, so that it would be in order to_ denote the lipoids
rather as persistent bodies bequeathed from a period of their
growth, and consequently it follows that it would be no great
error to conclude that at this perioda secretion, such as was noticeable at the period that preceded it, either considerably declines
or entirely disappears. However, in the various cells which
belong to the latter class, the afore-mentioned secretory functions are developed to the extreme throughout all their growth,
and there is an appearance which points to the utter exhaustion of plastosomes‘ on account of these functions. From the
 
f scantiness of ‘materials, it is diflicult to determine the destiny
 
of this kind of cells; whether the cell body ultimately breaks
up and decays or is absorbed or whether after throwing out
the secretions, the plastosomes again increase or are replenished, and thus it slowly passes into the former class of
cells; however, I at least am confident that it would be prema
ture to assert that the various periods illustrated stand for M
 
a direct indication of retrogression or decay. In short, in the
larger-typed decidual cells, it is possible clearly to observe in
a portion of them the same process of secretion as in the small type cells, whereas in the largest number there is almost no
sign of such a function, which fact _is worth much attention.
 
The large-type decidual cells, as aforesaid,~ no longer present
the ordinary phenomena of - secretion for the most part, and yet,
at a certian period, dark-stained coarse granular bodies of ir
regular sizes often make their appearance within the bordering
membrane of the periphery (figs. 55, 59 to 61); various material
products having the same staining properties are often detected within the interstitium (figs. 70 and 71), which makes
one feel that there is a certain formative relation between the
two. And, ‘besides, similar products often filling up the blood
vessels around them, - give’ the appearance of being absorbed
in the vascular organs (fig. 71). Such peculiar products having been originally observed in the fixed preparations, it follows
that they might be an artificial product, a result of the fixatives,
and yet from the observations mentioned above it is not difficult to conclude that a certain material which corresponds to them
is prepared, perhaps by some special function of the cell membrane of_the cell concerned, and is sent forth in the direction of
the interstitium. And should this supposition prove correct,
it would follow that these two kinds of large-type decidual
cells are functionally quite independent of one another, though
they are genetically of the same origin.
 
Looking on the whole of the functions of the decidual cells
from the histological point of View given above, I am led to believe that they may be roughly divided into three periods, according to the course of their development. The first period
is seen in all the small-typed decidual cells, the intermediate
type so termed by me, and in" a portion of the large—typed cells,
here the secreting functions are distinctly performed in the
same manner as in the stroma cells of villi. In the second
period, possibly by the functions of the cell membrane, a certain
product is prepared, to be sent forth in the direction of the
interstitium. The third period begins after the sixth month of
pregnancy, when the cell ‘body in general shrinks considerably,
and no plastosomes are to _be discovered, besides no particular
tissue structures from which inference may be made of the
functions performed are to be recognized. And, moreover, cells at this period experience the rise of embryon al pressure (the inner
pressure of the uterus) as the time of pregnancy elapses, in consequence of which they are remarkably flattened and afterwards
present the appearance of flattened epithelium. And,’ as regards
the destiny of decidual cells, it seems that it has been argued
 
‘in the past that they retrograde and perish by fatty degenera
tion or coagulative necrosis (Klein); however, as a matter of
fact, I have not as yet discovered such a change. All kinds of
decidual cells perfect their growth comparatively rapidly early
in the beginning of pregnancy, viz., in about threeweeks after
pregnancy, and after that only a quantitative increase or
decrease of the various cells occurs. Consequently, the degree
of growth of the cells cannot be the sole measure of the time of
pregnancy.’ However, judging from their quantitative relations, it is not difficult to arrive by Way of inference at the
approximate period of pregnancy; that is to say, the small type
cells appear from about the second week of pregnancy to the end
of the first month, and the intermediate-type cells from above
the seventeenth or eighteenth day to the end of the second month,
in both cases in exceedingly large numbers, while the large
type cells appear throughout the whole remaining period beginning about the twenty-second or twenty-third day of pregnancy,
and yet it will be noted that these large cells are at the height
of their activity during the period from the end of the first month
to the end of the third month of pregnancy, and while in the
fourth month the functions are still pretty high, they considerably decline in the months to follow, and in the seventh month
and after it is very seldom that such functions are clearly
noticeable. .
 
The phenomena of secretion of cells in the decidua serotina
in the first half of pregnancy _are nearly the same as in the
decidua vera as described above. "In the second half, especially
after the eighth month, giant-cells grow in large numbers, and
somewhat remarkable changes take place, even histologically
in the ordinary sense of the term, and, therefore, I have examined
the subject with an especially keen interest; however, the
absence of good materials, coupled with the difficulty in staining them has hindered me in. making excellent preparations, and the functions of cells at this period are therefore set aside
for future investigations.
 
5. The phenomena of secretion in the uterine glandular cells at the
time of pregnancy
 
The epithelium of the uterine gland undergoes a remarkable
change in the early part of pregnancy, Viz., on about the seventeenth or eighteenth day after conception (figs. 72 to 83). Now,
if we consider its phenomena of secretion, we shall find that,
even in this cell, lipoid granules first appear, and then vacuoles
are formed. In the stained preparations, lipoid granules appear
assembled and are accumulated especially near the basal part of
the cell body and show a remarkably clear yellowish-brown color
(figs. 73 to 78). The latter often appearing as contents of vacuoles
(figs. 77 and 78), it wouldprobably appear that the vacuoles are
a modified product of the lipoids, just the same as in the other
cases. In this way the lipoids gradually change into vacuoles,
the cell grows in size and presents a highly honeycomb structure
(figs. 77 to 80). The plastosomes either decrease in quantity or
become very difficult to discover as the functions of secretion
increase in activity. However, I have not been able to make
clear the formative relations between the plastosomes and
 
» lipoid granules. Be that as it may, it happens that, with the
 
increase of the function of secretion and the growth of the cells,
the latter gradually move over toward the comparatively enlarged
glandular lumen, and, at last, leaving the wall of the glandular
tubule, are entirely free Within the glandular lumen. The
characteristics of these desquamated cells are that either
the cell body shows a highly vacuolar formation or that the
vacuoles being somewhat reduced in quantity, theprotoplasm
becomes dark and turbid, and no plastosomes are to be found.
The condition of the nucleus is also exceedingly abnormal (figs.
 
‘ 81 to 83). How the various cells of this kind are broken up
 
by degrees and added to the large quantity of fragments filling
 
up the glandular lumen can be observed and followed with a
 
great certainty. '
The various changes of the uterine glandular cells as described above have, as was mentioned in my own observations, a
definite relation to the time of pregnancy, and accordingly
the rise and’ fall of the functions of secretion of these cells also
act upon it; that is to say that, in the first month and the first
half of the second month of pregnancy, the functions are at the
height of their activity, and they subside considerably from the
beginning of the third month, the subsidence being by far the
greater in the fourth month, and in the fifth month they seem
to come to a standstill, it being no longer possible to demonstrate the function of secretion in the months that follow, viz.,
in the second half of pregnancy. In the next place, the aforementioned functions of the glandular cells, as compared with
the decidua vera, appear more speedily and in a still higher
degree in the decidua serotina, and fail accordingly earlier than
in the former, and everybody easily recognizes that the scoretions of the glandular cell and its broken-up matter both accumulate in the glandular lumen for a certain period, though
some consideration should be given the question as to how
they are removed or absorbed. It is said that, according to
what has been written on this subject, the placental formation
commences from the second month and is perfected in the
fourth month and that the decidua reflexa and decidua Vera are
agglutinated in the fifth month. Should this opinion be true,
it would follow that the secretions of the uterus, looked at
from the periodic relations of secretion, are for the most part
drained into the uterine cavity, and take a part in the forma
' tion of the so-called uterine milk. However, according to my own
 
experience, it appears that the placental formation and the
adhesion of the decidua reflexa take part in an earlier part of
pregnancy. ,Therefore, I am inclined to believe that a part of the
secretions and detritus of the uterine glands, at least in a little
advanced period of pregnancy, are naturally absorbed by the
mother on account of the closure of the ducts.
 
SUMMARY
 
It is to be observed that the syncytium layer, Langhans’ cells,
stroma cells of villi, decidual cells, and uterine glandular cells,
all of which constitute the chief tissue elements of the placenta and decidua, each contained plastosomes as a constant ingredient of its protoplasm, and that a majority have at the same
time a certain quantity of either lipoid granules or vacuoles,
or of both, and, consequently the minutes histological structure
of these cell groups bears a close resemblance to that of
both the internally and externally secreting cells. And, moreover, these main components of protoplasm or cell body are,
according to their functions, as closely correlated to one another
as they are in the glandular cells. Now, taking a general survey of this correlation, it was found in my study that the plastosomes, being the first constituent, appear for the most to be
the matrix of lipoid granules from which the latter rise, and as
ia proof of this argument, I will cite the stroma cells of villi,
in which the correlation between the two is very closely shown.
We can notice it somewhat in the Langhans’ and decidual cells,
and if we closely examine the manner in which the lipoids appear
in these cells, it will be found that they always rise from granular bodies which are ‘very small and strongly siderophil. I
believe that these may be rightly compared with the so-called
‘Primargranulis’ which Heidenhain found in the common
glandular cells, and even though they appear very small, they
do appear as a perceptible body. There is no evidence to be
found of their appearing as slowly growing and increasing, as
Heidenhain assumes to be the case, from an infinitely small
body which is hardly seen microscopically until they enter the
vision of a microscope. Rather is it found that some of them
bear a close resemblance to the granular plastosomes in their
size and staining properties, clearly indicative of images running
over between the two (figs. 28, 29, 31, 36, and 42), which will
account for my argument that plastosomes should be deemed
the matrix of the lipoid formation. And, for the second rea
-son, I will give the fact that the plastosomes, either being con
siderably reduced in their quantity or having gone out of existence, as the lipoid forrnation progresses, are scarcely detected.
Such is the fact which is often noticed in all the cell groups
other than the stroma cells of villi, and a part or the whole of
the plastosomes cannot but be seen as having been consumed or exhausted in the formation of lipoids. However, in the Langhans’ cells, the stroma cells of villi, and in the decidual cells
sometimes, when the functions have advanced considerably,
the plastosomes not only show no sign of their decrease, but
also increase and present more or less conspicuous groups in a
limited section of the cell body. This apparently contradicts
the statement given above, but, practically, the reverse is the
case. It is probable that the plastosomes consumed partly by
the functions performed, are increased and replenished, providing for the repetition of secondary and tertiary functions; by
such an assumption the significance of the increase of plastosomes
in these cases will be made naturally clear, so that the various
 
‘ images described above do support with more force, instead of
 
contradicting, the theory mentioned above.
 
And then, the lipoid granules growing and enlarging, as they
do, from the very small granular bodies described above, change
more or less in quality at the same time, and their color becomes
somewhat faint, and, moreover, in certain cells, as for instance
in a part of the epithelium of the uterine gland and the largetype decidual cells, they sometimes appear as granules having a very clear yellowish-brown color. At any rate, when they
reach a certain degree of development, these lipoid granules
create more or less conspicuous halos around themselves, which
gives them the appearance of the contents of vacuoles. Such
appearances_ are very commonly noticed in all the cell groups
I have examined, and I cannot help recalling to mind the observations made by Babkin, Rubaschkin, and Ssawitsch respecting pancreatic cells as- cited before. Therefore, I believe that
this appearance has a very great significance in the secretion
formation, in the same way as the phenomena of secretion of
 
the pancreas as interpreted by these three observers just
 
referred to does. In other words, the lipoids may be compared
with the secretory granules of ordinary cells, and they like the
latter are slowly liquefied, in accordance with the third one of the
various forms of glandular secretion (liquefaction) described
above, and pass over to the secretions of a vacuolar shape. Therefore, the vacuoles are, after all, nothing else but a modified product of lipoids, and the contents should possibly be secretions
as transparent as water.
 
According to the arguments given above, the various cellgroups of the -placenta and decidua entirely agree with the observations of the glandular cells not only in their structure, but
also in the histological changes that follow their functions, and,
therefore, there is no room for doubt that secretion should
be existent in them also. And it will be briefly stated, concerning their secreting phenomena, that probably lipoid granules rise directly from plastosomes, and then the former, growing in size, slowly change to the vacuoles, viz., secretions,
and are thus thrown out of the cell body at times. If looked
at from the standpoint of their secretion formation these cells,
for the most part, closely resemble the external secretory cells,
but viewed with regard to their inner structure in which they
keep secretions within their own bodies for a comparatively long
period and thus for the most part present a more or less conspicuous foamy image, they should be rather compared with the
various internal secretory cells, which are observed in the ovary
and the cortex of suprarenals. The principles of the phenomena
of secretion, as aforesaid, look very simple indeed, and yet these
phenomena do not make their appearance in one and the same
cell necessarily at the same time. On the contrary, it is customary that within different parts of the same cell body the
various stages of phenomena appear, one after the other, in consequence of which the structure of each individual cell becomes
comparatively complex and diverse. Each individual cell, while
repeatedly performing its secreting functions in this manner,
gradually increase in itssize, and it is customary for the cell to
grow considerably as it reaches the height of secretion. Even
the syncytium layer whose cell border is indistinct, is generally
very thick at the height of secretion, and the gradual increase
in the size of the cell along with the rise of its secreting functions
in this manner may be partly due to the accumulated assemblage
of the secretions, though at the same time it cannot be denied
that the rise of secreting functions is attended by the increase
of the protoplasm and the growth of the nucleus.
 
 
There is, of course, a certain limit to the growth of each cell,
but there is something exceptional about the decidual cell. It
rises from certain extraordinarily small spherical cells within
the proper mucous membrane of uterus, and yet it grows so
very rapidly and becomes enormous in size that the classification between the large and small types in the ordinary decidual cells, if dealt with according to their genesis, shouldbe anything but significant. For these two mutually run over to
one another through the intervention of the intermediate
type, and no sharp demarcation exists between them. Therefore, these two kinds, histogenetically, belong to exactly the
same kind of cell, and they only differ in that one is still young
in its growth while the other has already perfected its growth.
However, it must be noted here particularly that the two present an entirely different appearance histologically, and, therefore, in all probability, along lines‘ of their physiological
functions. In other words, the decidual cell entirely changes its
structure and functions along with the perfection of its growth.
That is to say, the decidual cellwhich has perfected its growth
no more demonstrates within its body any important tissue ingredients, except plastosomes; however, it seems that probably,
at this period, the cell prepares, by means of the special action
of a very strongly developed cell membrane, certain secretions,
and sends them forth into the interstitium. At any rate, the cell
passing through this stage gradually withers and becomes smaller.
 
The secretions, while at the height of their formation, are
conglutinated with one another, produce in abundance vacuoles of various sizes and shapes, and will show a high beehive
structure. And the way of their removal and absorption, if
in the syncytium layer, will be, undoubtedly, by rupture, sooner
or later, toward the intervillous spaces, and thus they will be
absorbed in the mother’s blood, while in the various other cells,
there is no knowing but that the secretions are thrown out by
osmosis, and the secretions of the Langhans’ cells and the stroma
cells of villi should, as a matter of course, be absorbed on the side
of embryo, with the exception of those, which, finding their outlets in the Langhans’ islets, are probably taken in by the mother’s body. Both the large and small types of decidual cells certainly belong to the mother’s side, and the secreted or brokenup matter of the uterine glandular cells is at first probably
drained into the uterine cavity, to be absorbed by the mother’s
side. And, on comparing the relations between the secretion of
these Various cells, and the time of pregnancy we find that, in
general, the secretion is at its height in the first half of pregnancy, and especially in the early part of that period, whereas
in the second half of pregnancy it generally declines considerably, it being possible to demonstrate it only for a certain
period in the stroma cells of villi, the cells of Langhans’ islets,
and in the decidual cells. Below I will give this correlation
with a diagram.
 
In short, it may be deduced that all the important tissue elements of the placenta and decidua, if looked at from the histological View-point, perform secreting functions. Pending further investigations in all possible directions, it would be difficult to tell what significance these secretions thrown out of the
 
various cell groups have physiologically; however, since it is
evident that almost all of their secretions are internally rejected
and are taken in either by the mother’s or by the fetal side,
it makes one feel that, either by the cooperation of certain ‘hormones’ Which should of necessity be contained in each kind of
secretions or by their contending actions, both the mother and
the fetus would enjoy an extremely delicate and special
physiological action. If that is so, it follows that the placenta
should contain a great variety of ‘hormones,’ and the kind
and quantity of ‘hormones’ contained should naturally differ
according to the period of pregnancy and the kind of tissues,
it being quite clear from the following chart that, speaking
generally, those that are found in the early part of pregnancy
should be comparatively numerous in kind and in abundance.
On the contrary, however, I could not find any important
secretions in the placenta which is Well ripened. This is the
point to which I should like to call attention for the deliberate consideration of all observers who are interested in the placental poison.
 
 
 
THE MINUTE HISTOLOGICAL STRUCTURE AND PHENOMENA OF INTERNAL SECRETION IN THE UTERINE MUCOUS MEMBRANE PRIOR TO MEN SES
 
1. My own observations
 
a. The changes of the interstitial cells (figs. 84 to 91). The one
shown in figure 84 is an interstitial cell in normal condition,
it is Very small and ball-shaped,_ and the cell body as compared With its nucleus exceedingly small, containing within a
certain quantity of plastosomes which are largely rod—shaped.
 
A diagram shaurhvg the correlation between the secretion and the months of pregnancy in the various
cell groups of the human placenta and decidua
—_.j—_
oxozuva
 
Langlums’
cells
 
 
   
         
 
Lzmghans’
is] at s
 
Sliroma (tells
of villi
 
 
 
 
flncen! a foetalia
 
 
   
 
Small and intenncdiate
types
 
I urge type
__.4---_-1 _ ——
n the decxdua
serotina I
l I
 
   
 
   
   
 
Decidual
cells
 
   
   
 
Placenta uterine
and
decidua Vera
 
 
 
p-2.-:—
 
mumu:nu_ll§-—
 
White: Absorbed by mother.
Remarks: Black: Absorbed by fetus.
Striated: Thrown out of mother's body.
 
Glandular
cells
 
 
The nucleus is extremely clear and contains a nuclear network
and conspicuous nucleoli. Figure 85 is remarkably larger than
the former and is oval. The protoplasm increases in quantity
and so does the nucleus. Within the cell body there are no
plastosomes to be found, but, on the contrary, there are, in
large numbers, strongly black—stained and almost equally shaped
lipoid granules. The cell illustrated by figure 86 is filled by
large numbers of vacuoles Within the cell body, and Very little
is protoplasm proper. The plastosomes, being rod-shaped, for the most part lie scattered in the partition walls between the
vacuoles. ‘Besides, there are, in large numbers, strongly blackstained and almost equally shaped lipoid granules. The cell
illustrated by figure 86 is filled with large numbers of vacuoles
within the cell body, and there is little protoplasm proper.
The plastosomes, being rod-shaped, for the most part lie scattered
in the partition walls between the vacuoles. Besides, there are,
in various parts of the cell body, a few extremely small lipoid
granules, small in numbers. The nucleus is somewhat dark
and the nuclear network is indistinct. In this cell and those
that are enumerated below there is a somewhat distinct border
 
membrane on the surface.
 
In figure 87 both the cell body and nucleus are oval and,
though the structure of the cell body is similar in general to the
former, the lipoid granules appear in a somewhat larger quantity, in some cases existing as the contents of a vacuole. Now,
the vacuoles grow larger than in the former in general. The
plastosomes are comparatively few. In figures 88 and 89 both
the cell body and nucleus are somewhat dark in color. Within
there are vacuoles which appear in comparatively small numbers. The plastosomes in the one are somewhat larger in quantity and are distributed all over, while in the other they are comparatively smaller in number and are confined to a certain
section. Both demonstrate more or less lipoid granules of
various sizes. In figure 89 some of the lipoid granules contained
are light-colored, and it is extremely remarkable to find
the manner in which they present themselves as contents of
vacuoles. Figure 90 illustrates changes of a very high degree,
and the cell body is filled up with remarkably large numbers of
vacuoles of different sizes, while the plastosomes lie scattered,
in somewhat large numbers, in the partition walls of the vacuoles. The lipoid granules are extremely few in number and are
very small in size, while the nucleus» is grown in size considerably, is clear and has nuclear network and nucleole, both of
which are distinct. Figure 91 also shows nearly the same structure as the former, and yet its vacuoles being agglutinated with
one another in large numbers, form large and irregular—shaped cavities, in consequence of which the cell body appears as though
it were on the verge of destruction. There are no plastesomes to be detected, though the nucleus appears in a still full
and stained condition, and both the nuclear network and nucleoli are conspicuous.
 
b. The changes of the glandular cells (figs. .92 to .96). Figure
92 illustrates, for the:-sake of comparison, a normal glandular
cell, the nucleus is remarkably long and occupies the middle
part of the cell body, so that the celljfbody is divided into
the upper and basal parts, each being filled up with numberless plastosomes. The cilia are somewhat short and thick
and are not altogether normal. Figures 93 to 96 illustrate the
changes which take place prior to menses. Figure 93, as compared with normal conditions, is remarkably larger and its
nucleus, being relatively small, lies rather inclined to the base
of the cell, while the plastosomes, being chiefly short and rodshaped, largely lie scattered between the nucleus and the top of
the cell, it being a peculiarity of this cell that there are large
numbers of yellowish-brown lipoid granules assembled at its
basal part. Besides, there are in another part of the cell a
few deep-back lipoid granules, and, again, in this cell there
are extremely large numbers of vacuoles nearly of an equal
size, crowding together close to the top, viz., the cilial layer
of the cell body, though some vacuoles arrange themselves
along the surface of the nucleus in the deeper part of the
cell. In the cell illustrated by figure 94, the upper part of the
cell is clear, in general, because of the particularly conspicuous
vacuolar formations, whereas the common protoplasm is accumulated more or less in the basal two-thirds of the cell, viz.,
around the nucleus, in which part vacuoles are also detected, though they are for the most part very small. Besides,
in this protoplasmic part there are extremely large numbers
of plastosomes, which arrange themselves and crowd together in various directions. Again, yellowish-brown lipoid granules are found in comparatively small numbers in the basal part
of the cell, while deep-black lipoid granules, small in size and
numbers, lie scattered in the upper part of the cell. The nucleus is relatively clear, and its nuclear network is indistinct.
It is easy to find the traces of cilia in figures 93 and 94. In figure 95 there are absolutely no cilia to be found, and the upper
third of the cell is remarkably clear and is formed by somewhat
large numbers of vacuoles, whose partition walls, having disappeared in part, give them the form of very irregularly shaped
inner spaces. The lower two—thirds of the cell consist of remarkably dark protoplasm, and has in the middle a somewhat
large nucleus. Within the protoplasm there are numberless
vacuoles of a small size and comparatively small numbers of
plastosoines. Both the nuclear network and nucleoli are very
conspicuous. And this kind of cell is to be noticed in greatest
numbers during the changes of the glandular epithelium. The
cell shown in figure 96 is very weak in staining properties, both
in its cell body and nucleus, and its minute structure is by no
means ascertained. This kind of cell is very seldom seen, and may probably belong to the regressive type.
 
2. The phenomena of internal secretion
 
The so—called menstrual decidual cells are extremely varied
in their shape and size, and yet, if looked at from the minute
histological structure of the cell body, it will be noted that
plastosomes, lipoid granules, and vacuoles constitute their chief
components. The manner in which the latter, probably following the functions of the cell, correlate with one another may be
easily recognized as being in extreme agreement with what is
in the small-type decidual cell during pregnancy, and consequently, there is no. room for doubt that the functions of the
cells concerned are performed in the same manner as the latter.
Therefore, not only am I inclined positively to assert the existence of internally secreting functions even in the menstrual
decidual cells, but also I believe that the origin of these cells
is found in the interstitial cells proper of the uterine mucous
membrane, from which origin, gradually with the rise of the
function of secretion, a remarkable development and increase
of the nucleus and cell body such as is described above are brought about, the relation in this case being in exact coincidence
with the growth of the pregnant decidual cells. These facts
taken into consideration, I am convinced that the two kinds
of decidual cells (menstrual and pregnant) described above
have the same origin, and yet the cells being influenced by the
physiological conditions sometimes develop into the menstrual decidual cells, and sometimes, being advanced further,
run over to the pregnant decidual cells. _
 
And, on taking a glance at the epithelial changes of the uterine gland, we find that, as in the ordinary glandular cells, plastosomes, lipoid granules, and a large number of vacuoles, which
last may be deemed a modified product of lipoid granules,
are contained therein. The vacuoles grow in size gradually
and are finally fused and present a honeycomb structure,
especially on the surface of the cell, and then after losing the
cilia, the cells assume the appearance of goblet cells which have
their secreted matter accumulated chiefly on the surface.
Along with such changes, it will be noted, on the other hand, that
plastosomes and lipoid granules gradually diminish and disappear, and it appears that part of those cells which show changes
in a high degree die and perish. In short, these structural
changes cannot but clearly indicate the fact that these cells perform functions which are similar to the ordinary glandularcells.
And, on comparing these changes with those experienced in the
glandular cells during pregnancy, we find that the backward
ness in the degree of the appearance of lipoid granules and
vacuoles occurring in these cells makes one feel as though a
decided difference would exist between the two, however true
it may be that no radically great difference exists between them.
 
With regard to the periodic changes of the uterine mucous
membrane, ‘there have been many researches, such as the
investigations of Hitschman, Adler, and Schroder (’07).
Though a universally well-known fact, and yet confined chiefly
to the shape of the glandular tubules and the epithelium, very
few observers have so far paid attention to the functional
significance of the so-called ‘menstrual decidual cells which are
produced by the evolution of the interstitial cells, with the exception of Asada, who has quite recently demonstrated the existence of fat within the cells concerned, and inferred only that
this fat is not a degeneration product and must have some relation to the functions of the mucous membrane. However, according to my observations mentioned above, it is easy to clearly
recognize that, according to their structure, these cells also
have secreting functions as in the case of the ordinary decidual
cells. And, looked at from the histological View-point, I do not
hesitiate conclusively to pronounce that this function declines
and terminates immediately upon the beginning of the menses.
From want of suitable materials on hand, I am not able to make
a definite statement as to what destiny should befall these cells;
however, I quite agree with the observations of other investigators in that they suddenly diminish and perish with the
arrival of the menses. And, since it is doubtless true that the
secretions of these cells are absorbed in the mother’s
body, it should be a matter of special interest to consider the
several clinical symptoms which present themselves frequently at menstruation, in the light of this fact for ‘the explanation of their causative relations. On the contrary, the changes
of the uterine glandular epithelium, if compared at the time of
pregnancy are remarkably small, and as we can easily assert
that its secretions are thrown out of the body, there is certainly
no need for argument that it is impracticable to attach an
internal secretory significance to the glandular cells; therefore, I am inclined to believe that this sort of periodic changes
of glandular epithelium should be recongized as a mere preliminary behavior which is antecedent to pregnancy, and that by
far the greater significance, rather theoretically than functionally, should be attached to it.
 
CONCLUSION
 
1. The epithelium and stroma cells of villi, decidual cells,
and uterine glandular cells, all of which constitute the chief
tissue elements of the placenta and decidua, if subjected to the
closest cytological investigations, show within the cell bodies,
and common to them all, the formative constituents, such as plastosomes, lipoid granules, and vacuoles. These constituents, along with the functions of the cells, mutually show the
requisite correlation with which they are connected with one
another. Specifically:
 
a. The plastosomes, though for the most part rod-shaped,
are either long or short, but occasionally they are granular,
chain-like, or filar in their shapes. Their quantity generally
more or less diminishes along with the progress of the secreting
functions. .
 
b. The lipoid granules are extremely varied in their shape,
quantity, and in color (in the stained preparations), according
to cell or the group to which the cell belongs or perhaps in accordance with the difference in the period of functions. In the
earliest stage of their -appearance they are always granularshaped of extremely small size, and sometimes it is difficult to
distinguish them from the granular-shaped plastosomes (‘plastochondrin’), insomuch so that it _suggests that the plastosomes may exist in a direct formative participation as matrix of the
lipoid granules. And this connection is most conspicuously
demonstrated in the Langhans’ cells, the stroma cells of villi,
and in the decidual cells, and even in other cells it is quite
easy to recognize it, because the plastosomes tend to diminish
more or less in inverse proportion to the increase in the quantity of the lipoids. ,
 
c. The vacuoles are probably nothing but the lipoids
gradually liquefied and increased into what they are. And, with
 
the rise of functions, they keep increasing in numbers and, as.
 
a higher degree of activity is attained, the vacuoles grow in
size, and part of them by degrees become agglutined with one
another, so that at last the cell body presents in its entirety a
highly foamy image, being composed of numberless vacuoles of
various sizes.
 
The various cell groups mentioned above, if looked at from
their minute structure as well as the changes in the formative
components, which latter probably have an intimate connection with their functions, bear a close resemblance to the ordinary classical glandular cells (pancreas, salivary and lacrimal glands) and the important internal secretory cells (luteal and
interstitial cells of ovary, the cortical cells of suprarenals), and
there exists no radically great difference between the two.
That is to say, suppose we now take lipoid granules for secretory granules and vacuoles for secretions, and naturally these
cell groups in placenta and decidua should come under the same
category as glandular cells, and there would be no doubt whatever that the former have certain secreting functions in
themselves.
 
2. The secreting phenomena of placental and decidual cells,
with only the exception of the large-type decidual cells, generally present themselves as in the case of the ordinary glandular
cells, with the changes which commonly appear in the structure
of the cell bodies and almost under the same form. Now,
looked at from the histological viewpoint, the secretions prob
ably rise from the ‘plastochondrin,’ and then first passing
 
through the period of minor granules which corresponds to
Heidenhain’s ‘Primargranulis,’ they gradually grow in size
and form into the ordinary lipoid granules, which latter,
being liquefied continuously, change directly to the secretions
(vacuoles). And, in this matter, it seems that the series of
histological changes ordinarily even in the same cell body take
place at different times and in different regions, so that the
changes make their appearance in repetition secondarily, thirdly,
and so on, which fact is responsible for the intricacy of structure which sometimes occurs in certain cells.
 
3. The methods of discharging secretions, if in the syncytium layer, are that the vacuoles finally rupturing themselves
in several parts of the superficial layer cause their contents—secretions—to escape directly into the intervillous spaces in a
striking manner, though in the other cell groups the secretions
for the most part cannot but be recognized as passing out
by ‘osmose.’ And, of all the secretions, it should be noted
that those which come from the syncytium layer, decidual
cells, uterine glandular cells (a part) and also probably from the
Langhans’ islets are absorbed by the mother’s body, while
those which pass from the ordinary Langhans’ cells and the
stroma cells of villi are absorbed in the fetal side.
 
4. As regards the relation between the secreting functions
and the time of pregnancy:
 
a. The secreting functions of the syncytium layer may be
demonstrated from the beginning of pregnancy to about the
end of the fourth month, and yet it is in the second and third
months that they are most active. '
 
b. The secreting functions of the Langhans’cells are almost
entirely the same as in the sycytium layer. It is in the Langhans’ islets alone that they last somewhat longer, it being possible to demonstrate cells which have secretions in them up
to the fifth or seventh month, and naturally it can be imagined
that the functions continue up to that time.
 
c. The secreting functions of the stroma cells of villi begin
at about the end of the first month of pregnancy, and keep quite
active up to about the seventh month, though from the second to the sixth month they are at their height. However,
it should be noted with care that in the eighth month these
cells suddenly diminish remarkably and perish, in consequence
of which the functions also will drop promptly at this period-.
 
d. The decidual cells are entirely different in their appearance
falling in the classification into large and small types, as
it is well known. That is to say, in the so-called small—type
cells the secreting conditions pretty Well agree with those in the
other cells. This kind of cells appears already quite active on
about the seventeenth or eighteenth day after conception, and
nearly at the end of the first month of pregnancy its growth
and, consequently, its functions reach their climax. Thereafter, as the large-type decidual cells appear, the small—type
cells suddenly diminish in quantity, and in consequence it appears-that the functions also drop quickly, though even up to
the seventh month of pregnancy it is able to clearly demonstrate
the existence of the functions.
 
Then, in the so-called large-type decidual cells, for the most
part few, are the structures of the cell body by which the existence of secreting functions may be proved; however, in its
strongly developed cell membrane a certain substance is formed,
probably by a peculiar faculty of its own, and in this manner there occurs a material formation which may be deemed a
secreted matter which is excreted by the cell body.
 
The large—type decidual cells are remarkable in their appearance by the end of the first month of pregnancy, though
in the second month they appear to reach their climax, and in
the following third or fourth months, they diminish in their
size. And, the afore-mentioned secreting phenomenon which
is peculiar to these cells, begins in the second month, appears
most remarkably in the third month, and may be demonstrated
up to about the sixth month, though in the seventh month and
after it is no longer possible to observe it. In general, the
large-type cells retrograde and decay remarkably in the second
half of pregnancy, though at the end of pregnancy it is still
able to find them, and, moreover, at this period there are some
few cells which do contain a small quantity of lipoids.
 
The functions of the glandular epithelium are most active
at the end of the first month of pregnancy, begin to drop
considerably from the beginning of the third month, in the
fourth month the decline is greater, and in the fifth month, it
appears, they almost come to a standstill. In general, the
functions make their appearance somewhat earlier in the decidua
serotina than in the decidua Vera, and accordingly they stop
earlier in the former than in the latter. The secretions are
thrown out into the uterine cavity probably only in the earliest
period of pregnancy, and later as the openings of the glandular
tubules are closed by the placental formation and by the adhesion
of the decidua Vera and decidua -reflexa, the secretions, along
with the detrital matters of the degenerated glandular cells are,
of necessity, absorbed by the mother.
 
5. Since it is possible that the secretions of the various kinds
of cell groups mentioned above are, for the most part, absorbed,
either by the mother or by the fetus, as in the case of internal
secretions, everybody will easily assent to the supposition that,
like the secretions of many internal secretory glands, each of
them contains a certain hormone, and should this be the case,
it may be said that each of the two organs concerned is assuredly a producer of hormones of various sorts and kinds, and is also a reservoir for them; and the kinds of hormones and the proportion of their mixture as contents of these organs should
have important bearings upon the time of pregnancy and the
part of the organs concerned which is taken as material for
investigation. And, in the first half of pregnancy, it is possible to show quite a variety of hormones, whereas in a wellripe placenta it is almost impossible to demonstrate their
existence. ,
 
6. It has been believed by several authors that the epithehum of villi probably serves as an organ by which nutrition is
taken to the embryo; however, histologically it is impossible
to find any ground for such argument.
 
7. The various cells described above usually increase in size
more and more as their secreting functions progress. This
fact is most remarkably noticed in the decidual cells. The
large-type cell is, after all, nothing but the small-type cell
grown up; its growth being gradual along with the progress of
its functions and with its largest size it has perfected its development. Therefore, though at a glance it would seem that these
two kinds of cells are entirely different from one another, yet
they have the same origin, and originally they are the cells
of the same kind. However, the sharp demarcation which
exists between the two functionally should deserve our attention; that is to say, the decidual cell performs the conversion of
its functions along with the perfection of its growth.
 
8, The foregoing conclusions would, at a glance, seem to
contradict the work conducted by several authors up to now
whose conclusion it was almost entirely to deny the internal
secreting functions of the placenta and decidua; but the main
 
reason for this is the fact that the materials employed for ‘
 
investigation by these authors have been for the most part mature organs, for in these there is almost no proof of any secreting
phenomena being existent, and they have been therefore taken
at most unfavorable times as materials to help us attain our
aim. Therefore, in the future, should anyone desire to try
his hand in this sort of research, it would be necessary for
him by all means to take materials while yet in the early part of pregnancy. And, even in this case secretions of several
kinds, even if they come from cells of one and the same origin,
would possibly be, by no means, similar in quality, but rather
in the organ concerned, there would be existent various kinds
of substances produced from the various cell groups Whichform
the organ. And, in case that there is a certain hormone action
in these substances, it would follow that, during a certain period
of pregnancy, the hormones will act upon both the mother and
the fetus in diverse and complex manners.
 
9. The histological changes which the interstitial cells of the
uterine mucous membrane and glandular cells undergo prior
to menses resemble, in general, the changes which take place at
the beginning of pregnancy, though they are by far the weaker.
Therefore, even in that case, these two kinds of cells, looked
at from their histological structure, have in common to themselves, secreting functions, to whose existence we may positively
assert. And, the secretions, if in the interstitial cells, are undoubtedly absorbed internally, as in the case of the small-type
decidual cells while in pregnancy, and should thereby bring
about the various clinical symptoms which are experienced during menses.
 
The glandular cells differ from the former, and the secretions have probably no endocrine nature and are immediately
thrown out to the outside, viz., into the uterine cavity, so
that it would be difficult to attach to_ them an important
physiological signficance, such as hormone action. Rather, it
would be fit to interpret such periodical changes of these cells
as preliminary phenomenon of the coming pregnancy.
 
10. The interstitial cells of the uterus, prior to menses, are
developed into the so—called menstrual decidual cells, which in
point of structure, distinctly reminds us of the decidual cells
of pregnancy. For this reason, it would be in order for us to
trace the origin of the latter, as of the former, to the interstitial
cells of the uterus.
 
In conclusion, my whole-hearted gratitude goes to Prof.R.
 
'Tsukaguchi for the kind and sincere leadership and revision
 
which he has given me at the present Work, and to Professor
Ogata, chief of our gynecological department, for the valuable
materials for research and for the immense assistance he has
given me.
 
July, 1920.
 
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37.
 
ZIMMERMANN, K. W. 1898 Beitriige zur Kenntnis einiger Drfisen und Epithelien. Archiv f. Inikr. Anat., Bd. 52.
 
ZOYA, ,L. E R. 1891 Interno ai plastiduli fucsinofili (bioblasti dell’ Altmann).
Mem. del R. Ist. Lomb. de sci. e lett., vol. 12, cl delle Sc. mat. e
nat., cited from Heidenhain.
 
1891 Uber die fuchsinophilen Plastidulen. Archiv f. Anat. u. Phys.,
 
- Anat. Abt.
EXPLANATION OF PLATES
 
All the figures given on plates have been drawn at the height of the object
stage, by Abbe’s apparatus, under the same magnifying power: Zeiss’ 1LpOCllI‘0lI12Ll3
homogene immersion 3 mm., compensations okular. 12, tube length 160 mm.
 
The Various figures have all been drawn from the preparations fixed by Levi’s
solution and stained by Heidenl1ain’s iron—alum-haematoxylin, with only the
exception of figure 7, which has been reproduced from the preparations by Altmann’s method, after changing the color.
 
PLATE 1
 
EXPLANATION OF FIGURES
 
1 to 12 Illustrate the syncytium layer and a part of the Langhans’ cells. _
 
 
PLATE 2
EXPLANATION or FIGURES
 
13 to 26 Illustrate the Langhans’ cells.
 
27 to 38 The stroma cells in the chorion villi.
 
39_ to 69 The decidual cells.
 
70 The peculiar-looking product which makes its appearance in the cell
 
membrane and interstitium of the large-type decidual cells.
 
71 The above-mentioned product filling up the blood vessels.
 
72 to 83 The glandular epithelium during pregnancy.
 
84 to 91 The interstitial cells prior to menses.
 
92 to 96 The glandular epithelial cells prior to menses
 
 
 
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[[Category:Uterus]][[Category:Placenta]][[Category:Historic Embryology]][[Category:1920's]]

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